temporal scale score,spatial scale score,ecological scale score,genome scale score,spatiotemporal scale score,temporal scale category,spatial scale category,ecological scale category,genom scale category,study focus,scorer,Year Published,URL,Authors,Title,Publication Name,Volume,Beginning Page,End Page,Article Number,Digital Object Identifier (DOI),Abstract
1,3,1,6,4,none,small spatial scale (couple of populations),none - theoretical,exome/transcriptome,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1016/j.gene.2018.05.058,"Gawade, P; Ghosh, P",Genomics driven approach for identification of novel therapeutic targets in Salmonella enterica,GENE,668,211,220,,10.1016/j.gene.2018.05.058,"Salmonella enterica is a causative agent of enteric and systemic salmonellosis that affects human and many other animal species. Due to the emergence of drug-resistant strains, available drugs against S. enterica infection are no more effective as before. Thus, there is an urgent need to develop new therapeutic strategies. The current study aims at prioritizing therapeutic targets by an in-silico genomics driven method. The method involves searching proteins of each Salmonella strain for essentiality, virulence and antibiotic-resistance and host-pathogen protein protein interactions. Using subtractive genomics approach, we further confirmed that none of the selected protein shares sequence homology with any human (host) protein and also with proteins from human symbiotic gut flora. Pathway analysis of these screened proteins revealed associated biological processes. Presence of proteins in pathogen-specific pathways was used as one of the assessment property in the subsequent scoring scheme. Simultaneously proteins are screened based on parameters like druggability (sequence similarity with existing drug targets), sub-cellular localization and presence of transmembrane domain. The implemented scoring scheme depicted a final list of 14 potential therapeutic targets out of which 6 could be identified as 'high-confidence' targets based on extensive literature curation. Identified therapeutic targets can aid in the design and development of effective antibacterial agents against S. enterica. The genomics driven strategy adopted in this study can also be applied to screen therapeutic targets for other pathogens."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Kathrin Naepflin,2018,https://doi.org/10.3389/fgene.2018.00287,"Robledo, D; Gutierrez, AP; Barria, A; Yanez, JM; Houston, RD",Gene Expression Response to Sea Lice in Atlantic Salmon Skin: RNA Sequencing Comparison Between Resistant and Susceptible Animals,FRONTIERS IN GENETICS,9,,,287,10.3389/fgene.2018.00287,"Sea lice are parasitic copepods that cause large economic losses to salmon aquaculture worldwide. Frequent chemotherapeutic treatments are typically required to control this parasite, and alternative measures such as breeding for improved host resistance are desirable. Insight into the host-parasite interaction and mechanisms of host resistance can lead to improvements in selective breeding, and potentially novel treatment targets. In this study, RNA sequencing was used to study the skin transcriptome of Atlantic salmon (Salmo salar) parasitized with sea lice (Cahgus rogercresseyi). The overall aims were to compare the transcriptomic profile of skin at louse attachment sites and ""healthy"" skin, and to assess differences in gene expression response between animals with varying levels of resistance to the parasite. Atlantic salmon pre-smolts were challenged with C. rogercresseyi, growth and lice count measurements were taken for each fish. 21 animals were selected and RNA Seq was performed on skin from a louse attachment site, and skin distal to attachment sites for each animal. These animals were classified into family-balanced groups according to the traits of resistance (high vs. low lice count), and growth during infestation. Overall comparison of skin from louse attachment sites vs. healthy skin showed that 4,355 genes were differentially expressed, indicating local up-regulation of several immune pathways and activation of tissue repair mechanisms. Comparison between resistant and susceptible animals highlighted expression differences in several immune response and pattern recognition genes, and also myogenic and iron availability factors. Components of the pathways involved in differential response to sea lice may be targets for studies aimed at improved or novel treatment strategies, or to prioritize candidate functional polymorphisms to enhance genomic selection for host resistance in commercial salmon breeding programs."
1,1,3,6,2,none,no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1038/s41598-018-30064-x,"Holtappels, M; Noben, JP; Van Dijck, P; Valcke, R",Fire blight host-pathogen interaction: proteome profiles of Erwinia amylovora infecting apple rootstocks,SCIENTIFIC REPORTS,8,,,11689,10.1038/s41598-018-30064-x,"Fire blight, caused by the enterobacterium Erwinia amylovora, is a destructive disease, which can affect most members of the Rosaceae family. Since no significant genomic differences have been found by others to explain differences in virulence, we used here a gel-based proteomic approach to elucidate mechanisms and key players that allow the pathogen to survive, grow and multiply inside its host. Therefore, two strains with proven difference in virulence were grown under controlled conditions in vitro as well as in planta (infected apple rootstocks). Proteomic analysis including 2DE and mass spectrometry revealed that proteins involved in transcription regulation were more abundant in the in planta condition for both strains. In addition, genes involved in RNA processing were upregulated in planta for the highly virulent strain PFB5. Moreover, the upregulation of structural components of the F0F1-ATP synthase are major findings, giving important information on the infection strategy of this devastating pathogen. Overall, this research provides the first proteomic profile of E. amylovora during infection of apple rootstocks and insights into the response of the pathogen in interaction with its host."
5,4,8,7,9,speciation time (small tree),species range,multiple species in the wild - environment constant,whole genome,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1016/j.ijpara.2018.03.010,"Knowles, DP; Kappmeyer, LS; Haney, D; Herndon, DR; Fry, LM; Munro, JB; Sears, K; Ueti, MW; Wise, LN; Silva, M; Schneider, DA; Grause, J; White, SN; Tretina, K; Bishop, RP; Odongo, DO; Pelzel-McCluskey, AM; Scoles, GA; Mealey, RH; Silva, JC","Discovery of a novel species, Theileria haneyi n. sp., infective to equids, highlights exceptional genomic diversity within the genus Theileria: implications for apicomplexan parasite surveillance",INTERNATIONAL JOURNAL FOR PARASITOLOGY,48,679,690,,10.1016/j.ijpara.2018.03.010,"A novel apicomplexan parasite was serendipitously discovered in horses at the United States - Mexico border. Phylogenetic analysis based on 18S rDNA showed the erythrocyte-infective parasite to be related to, but distinct from, Theileria spp. in Africa, the most similar taxa being Theileria spp. from waterbuck and mountain zebra. The degree of sequence variability observed at the 18S rDNA locus also suggests the likely existence of additional cryptic species. Among described species, the genome of this novel equid Theileria parasite is most similar to that of Theileria equi, also a pathogen of horses. The estimated divergence time between the new Theileria sp. and T. equi, based on genomic sequence data, is greater than 33 million years. Average protein sequence divergence between them, at 23%, is greater than that of Theileria parva and Theileria annulata proteins, which is 18%. The latter two represent highly virulent Theileria spp. of domestic cattle, as well as of African and Asian wild buffalo, respectively, which differ markedly in pathology, host cell tropism, tick vector and geographical distribution. The extent of genome-wide sequence divergence, as well as significant morphological differences, relative to T. equi justify the classification of Theileria sp. as a new taxon. Despite the overall genomic divergence, the nine member equi merozoite antigen (EMA) superfamily, previously found as a multigene family only in T. equi, is also present in the novel parasite. Practically, significant sequence divergence in antigenic loci resulted in this undescribed Theileria sp. not being detectable using currently available diagnostic tests. Discovery of this novel species infective to equids highlights exceptional diversity within the genus Theileria, a finding with serious implications for apicomplexan parasite surveillance. Published by Elsevier Ltd on behalf of Australian Society for Parasitology."
4,3,6,5,7,many generations,small spatial scale (couple of populations),single species in the wild - environment constant,"reduced representation of genome (RAD-seq, GBS, Seq capture)",both,Kathrin Naepflin,2018,https://doi.org/10.3389/fgene.2018.00266,"Naret, O; Chaturvedi, N; Bartha, I; Hammer, C; Fellay, J",Correcting for Population Stratification Reduces False Positive and False Negative Results in Joint Analyses of Host and Pathogen Genomes,FRONTIERS IN GENETICS,9,,,266,10.3389/fgene.2018.00266,"Studies of host genetic determinants of pathogen sequence variations can identify sites of genomic conflicts, by highlighting variants that are implicated in immune response on the host side and adaptive escape on the pathogen side. However, systematic genetic differences in host and pathogen populations can lead to inflated type I (false positive) and type II (false negative) error rates in genome-wide association analyses. Here, we demonstrate through a simulation that correcting for both host and pathogen stratification reduces spurious signals and increases power to detect real associations in a variety of tested scenarios. We confirm the validity of the simulations by showing comparable results in an analysis of paired human and HIV genomes."
2,1,2,3,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,gene family/microsatellites,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1371/journal.pone.0200585,"Batista, DFA; Neto, OCD; de Almeida, AM; Maboni, G; de Carvalho, TF; de Carvalho, TP; Barrow, PA; Berchieri, A",Evaluation of pathogenicity of Salmonella Gallinarum strains harbouring deletions in genes whose orthologues are conserved pseudogenes in S. Pullorum,PLOS ONE,13,,,e0200585,10.1371/journal.pone.0200585,"The diseases caused by Salmonella Gallinarum and S. Pullorum in chickens known as fowl typhoid and pullorum disease, respectively, pose a great threat to the poultry industry mainly in developing countries, since they have already been controlled in the developed ones. These bacteria are very similar at the genomic level but develop distinct host-pathogen relationships with chickens. Therefore, a deep understanding of the molecular mechanisms whereby S. Gallinarum and S. Pullorum interact with the host could lead to the development of new approaches to control and, perhaps, eradicate both diseases from the chicken flocks worldwide. Based on our previous study, it was hypothesised that metabolism-related pseudogenes, fixed in S. Pullorum genomes, could play a role in the distinct host-pathogen interaction with susceptible chickens. To test this idea, three genes (idnT, idnO and ccmH) of S. Gallinarum str. 287/91, which are pseudogenes on the S. Pullorum chromosomes, were inactivated by mutations. These genetically engineered strains grew well on the solid media without any colony morphology difference. In addition, similar growth curves were obtained by cultivation in M9 minimal medium containing D-gluconate as the sole carbon source. Infection of chickens with idnTO mutants led to increased numbers of bacteria in the livers and spleens at 5 days post-infection, but with slightly decreased heterophil infiltration in the spleens when compared to the wild-type strain. On the other hand, no significant phenotypic change was caused by mutation to ccmH genes. Apart from the above-mentioned alterations, all S. Gallinarum strains provoked similar infections, since mortality, clinical signs, macroscopic alterations and immune response were similar to the infected chickens. Therefore, according to the model applied to this study, mutation to the idnTO and ccmH genes showed minor impact on the fowl typhoid pathogenesis and so they may be relics from the ancestor genome. Our data hints at a more complex mechanism driving the distinct host-pathogen interaction of S. Gallinarum/Pullorum with chickens than differential inactivation of a few genes."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1128/mSphere.00228-18,"Sanders, BE; Umana, A; Lemkul, JA; Slade, DJ",FusoPortal: an Interactive Repository of Hybrid MinION-Sequenced Fusobacterium Genomes Improves Gene Identification and Characterization,MSPHERE,3,,,e00228-18,10.1128/mSphere.00228-18,"Here we present FusoPortal, an interactive repository of Fusobacterium genomes that were sequenced using a hybrid MinION long-read sequencing pipeline, followed by assembly and annotation using a diverse portfolio of predominantly open-source software. Significant efforts were made to provide genomic and bioinformatic data as downloadable files, including raw sequencing reads, genome maps, gene annotations, protein functional analysis and classifications, and a custom BLAST server for FusoPortal genomes. FusoPortal has been initiated with eight complete genomes, of which seven were previously only drafts that ranged from 24 to 67 contigs. We have showcased that the genomes in FusoPortal provide accurate open reading frame annotations and have corrected a number of large (>3-kb) genes that were previously misannotated due to contig boundaries. In summary, FusoPortal (http://fusoportal.org ) is the first database of MinION-sequenced and completely assembled Fusobacterium genomes, and this central Fusobacterium genomic and bioinformatic resource will aid the scientific community in developing a deeper understanding of how this human pathogen contributes to an array of diseases, including periodontitis and colorectal cancer. IMPORTANCE In this report, we describe a hybrid MinION whole-genome sequencing pipeline and the genomic characteristics of the first eight Fusobacterium strains deposited in the FusoPortal database. This collection of highly accurate and complete genomes drastically improves upon previous multicontig assemblies by correcting and newly identifying a significant number of open reading frames. We believe that the availability of this resource will result in the discovery of proteins and molecular mechanisms used by an oral pathogen, with the potential to further our understanding of how Fusobacterium nucleatum contributes to a repertoire of diseases, including periodontitis, preterm birth, and colorectal cancer."
1,2,6,7,3,none,local (one population),single species in the wild - environment constant,whole genome,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1128/mSphere.00269-18,"Todd, SM; Settlage, RE; Lahmers, KK; Slade, DJ",Fusobacterium Genomics Using MinION and Illumina Sequencing Enables Genome Completion and Correction,MSPHERE,3,,,e00269-18,10.1128/mSphere.00269-18,"Understanding the virulence mechanisms of human pathogens from the genus Fusobacterium has been hindered by a lack of properly assembled and annotated genomes. Here we report the first complete genomes for seven Fusobacteriurn strains, as well as resequencing of the reference strain Fusobacteriurn nucleatum subsp. nucleatum ATCC 25586 (total of seven species; total of eight genomes). A highly efficient and cost-effective sequencing pipeline was achieved using sample multiplexing for short-read Illumina (150 bp) and long-read Oxford Nanopore MinION (>80 kbp) platforms, coupled with genome assembly using the open-source software Unicycler. Compared to currently available draft assemblies (previously 24 to 67 contigs), these genomes are highly accurate and consist of only one complete chromosome. We present the complete genome sequence of F. nucleatum subsp. nucleatum ATCC 23726, a genetically tractable and biomedically important strain and, in addition, reveal that the previous F. nucleatum subsp. nucleatum ATCC 25586 genome assembly contains a 452-kb genomic inversion that has been corrected using our sequencing and assembly pipeline. To enable genomic analyses by the scientific community, we concurrently used these genomes to launch FusoPortal, a repository of interactive and downloadable genomic data, genome maps, gene annotations, and protein functional analyses and classifications. In summary, this report provides detailed methods for accurately sequencing, assembling, and annotating Fusobacteriurn genomes, while focusing on using open-source software to foster the availability of reproducible and open data. This resource will enhance efforts to properly identify virulence proteins that may contribute to a repertoire of diseases that includes periodontitis, preterm birth, and colorectal cancer. IMPORTANCE Fusobacteriurn spp. are Gram-negative, oral bacteria that are increasingly associated with human pathologies as diverse as periodontitis, preterm birth, and colorectal cancer. While a recent surge in F. nucleatum research has increased our understanding of this human pathogen, a lack of complete genomes has hindered the identification and characterization of associated host-pathogen virulence factors. Here we report the first eight complete Fusobacterium genomes sequenced using an Oxford Nanopore MinION and Illumina sequencing pipeline and assembled using the open-source program Unicycler. These genomes are highly accurate, and seven of the genomes represent the first complete sequences for each strain. In summary, the FusoPortal resource provides a publicly available resource that will guide future genetic, bioinformatic, and biochemical experiments to characterize this genus of emerging human pathogens."
1,2,6,7,3,none,local (one population),single species in the wild - environment constant,whole genome,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1128/AEM.00136-18,"Jibrin, MO; Potnis, N; Timilsina, S; Minsavage, GV; Vallad, GE; Roberts, PD; Jones, JB; Goss, EM",Genomic Inference of Recombination-Mediated Evolution in Xanthomonas euvesicatoria and X-perforans,APPLIED AND ENVIRONMENTAL MICROBIOLOGY,84,,,UNSP e00136-18,10.1128/AEM.00136-18,"Recombination is a major driver of evolution in bacterial populations, because it can spread and combine independently evolved beneficial mutations. Recombinant lineages of bacterial pathogens of plants are typically associated with the colonization of novel hosts and the emergence of new diseases. Here we show that recombination between evolutionarily and phenotypically distinct plant-pathogenic lineages generated recombinant lineages with unique combinations of pathogenicity and virulence factors. Xanthomonas euvesicatoria and Xanthomonas perforans are two closely related lineages causing bacterial spot disease on tomato and pepper worldwide. We sequenced the genomes of atypical strains collected from tomato in Nigeria and observed recombination in the type III secretion system and effector genes, which showed alleles from both X. euvesicatoria and X. perforans. Wider horizontal gene transfer was indicated by the fact that the lipopolysaccharide cluster of one strain was most similar to that of a distantly related Xanthomonas pathogen of barley. This strain and others have experienced extensive genomewide homologous recombination, and both species exhibited dynamic open pangenomes. Variation in effector gene repertoires within and between species must be taken into consideration when one is breeding tomatoes for disease resistance. Resistance breeding strategies that target specific effectors must consider possibly dramatic variation in bacterial spot populations across global production regions, as illustrated by the recombinant strains observed here. IMPORTANCE The pathogens that cause bacterial spot of tomato and pepper are extensively studied models of plant-microbe interactions and cause problematic disease worldwide. Atypical bacterial spot strains collected from tomato in Nigeria, and other strains from Italy, India, and Florida, showed evidence of genomewide recombination that generated genetically distinct pathogenic lineages. The strains from Nigeria and Italy were found to have a mix of type III secretion system genes from X. perforans and X. euvesicatoria, as well as effectors from Xanthomonas gardneri. These genes and effectors are important in the establishment of disease, and effectors are common targets of resistance breeding. Our findings point to global diversity in the genomes of bacterial spot pathogens, which is likely to affect the host-pathogen interaction and influence management decisions."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1186/s12864-018-4817-4,"Angelini, RMD; Abate, D; Rotolo, C; Gerin, D; Pollastro, S; Faretra, F","De novo assembly and comparative transcriptome analysis of Monilinia fructicola, Monilinia laxa and Monilinia fructigena, the causal agents of brown rot on stone fruits",BMC GENOMICS,19,,,436,10.1186/s12864-018-4817-4,"Background: Brown rots are important fungal diseases of stone and pome fruits. They are caused by several Monilinia species but M. fructicola, M. laxa and M. fructigena are the most common all over the world. Although they have been intensively studied, the availability of genomic and transcriptomic data in public databases is still scant. We sequenced, assembled and annotated the transcriptomes of the three pathogens using mRNA from germinating conidia and actively growing mycelia of two isolates of opposite mating types per each species for comparative transcriptome analyses. Results: Illumina sequencing was used to generate about 70 million of paired-end reads per species, that were de novo assembled in 33,861 contigs for M. fructicola, 31,103 for M. laxa and 28,890 for M. fructigena. Approximately, 50% of the assembled contigs had significant hits when blasted against the NCBI non-redundant protein database and top-hits results were represented by Botrytis cinerea, Sclerotinia sclerotiorum and Sclerotinia borealis proteins. More than 90% of the obtained sequences were complete, the percentage of duplications was always less than 14% and fragmented and missing transcripts less than 5%. Orthologous transcripts were identified by tBLASTn analysis using the B. cinerea proteome as reference. Comparative transcriptome analyses revealed 65 transcripts over-expressed (FC >= 8 and FDR <= 0.05) or unique in M. fructicola, 30 in M. laxa and 31 in M. fructigena. Transcripts were involved in processes affecting fungal development, diversity and host-pathogen interactions, such as plant cell wall-degrading and detoxifying enzymes, zinc finger transcription factors, MFS transporters, cell surface proteins, key enzymes in biosynthesis and metabolism of antibiotics and toxins, and transposable elements. Conclusions: This is the first large-scale reconstruction and annotation of the complete transcriptomes of M. fructicola, M. laxa and M. fructigena and the first comparative transcriptome analysis among the three pathogens revealing differentially expressed genes with potential important roles in metabolic and physiological processes related to fungal morphogenesis and development, diversity and pathogenesis which need further investigations. We believe that the data obtained represent a cornerstone for research aimed at improving knowledge on the population biology, physiology and plant-pathogen interactions of these important phytopathogenic fungi."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.3390/proteomes6020018,"Bittel, M; Gastiger, S; Amin, B; Hofmann, J; Burkovski, A",Surface and Extracellular Proteome of the Emerging Pathogen Corynebacterium ulcerans,PROTEOMES,6,,,18,10.3390/proteomes6020018,"Corynebacterium ulcerans is an emerging pathogen, which is increasingly recognized as an etiological agent of diphtheria, but can also evoke ulcers of the skin and systemic infections in humans. Besides man, the bacteria can colonize a wide variety of different animals, including cattle and pet animals, which might serve as a reservoir for human infections. In this study, surface-located proteins and the exoproteome of two Corynebacterium ulcerans strains were analyzed, since these may have key roles in the interaction of the pathogen with host cells. Strain 809 was isolated from a fatal case of human respiratory tract infection, while strain BR-AD22 was isolated from a nasal swap of an asymptomatic dog. While a very similar pattern of virulence factors was observed in the culture supernatant and surface protein fractions of the two strains, proteome analyses revealed a higher stability of 809 cells compared to strain BR-AD22. During exponential growth, 17% of encoded proteins of strain 809 were detectable in the medium, while 38% of the predicted proteins encoded by the BR-AD22 chromosome were found. Furthermore, the data indicate differential expression of phospholipase D and a cell wall-associated hydrolase, since these were only detected in strain BR-AD22."
1,2,3,7,3,none,local (one population),single species laboratory system - environmental aspect present,whole genome,Host,Kathrin Naepflin,2018,https://doi.org/10.1016/j.margen.2018.01.001,"Zueva, KJ; Lumme, J; Veselov, AE; Kent, MP; Primmer, CR",Genomic signatures of parasite-driven natural selection in north European Atlantic salmon (Salmo salar),MARINE GENOMICS,39,26,38,,10.1016/j.margen.2018.01.001,"Understanding the genomic basis of host-parasite adaptation is important for predicting the long-term viability of species and developing successful management practices. However, in wild populations, identifying specific signatures of parasite-driven selection often presents a challenge, as it is difficult to unravel the molecular signatures of selection driven by different, but correlated, environmental factors. Furthermore, separating parasite-mediated selection from similar signatures due to genetic drift and population history can also be difficult. Populations of Atlantic salmon (Salmo salar L.) from northern Europe have pronounced differences in their reactions to the parasitic flatworm Gyrodactylus salmis Malmberg 1957 and are therefore a good model to search for specific genomic regions underlying inter-population differences in pathogen response. We used a dense Atlantic salmon SNP array, along with extensive sampling of 43 salmon populations representing the two G. salaris response extremes (extreme susceptibility vs resistant), to screen the salmon genome for signatures of directional selection while attempting to separate the parasite effect from other factors. After combining the results from two independent genome scan analyses, 57 candidate genes potentially under positive selection were identified, out of which 50 were functionally annotated. This candidate gene set was shown to be functionally enriched for lymph node development, focal adhesion genes and anti-viral response, which suggests that the regulation of both innate and acquired immunity might be an important mechanism for salmon response to G. salmis. Overall, our results offer insights into the apparently complex genetic basis of pathogen susceptibility in salmon and highlight methodological challenges for separating the effects of various environmental factors."
3,3,3,5,6,few generations,small spatial scale (couple of populations),single species laboratory system - environmental aspect present,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Kathrin Naepflin,2018,https://doi.org/10.1111/jeb.13271,"Conlon, BH; Frey, E; Rosenkranz, P; Locke, B; Moritz, RFA; Routtu, J",The role of epistatic interactions underpinning resistance to parasitic Varroa mites in haploid honey bee (Apis mellifera) drones,JOURNAL OF EVOLUTIONARY BIOLOGY,31,801,809,,10.1111/jeb.13271,"The Red Queen hypothesis predicts that host-parasite coevolutionary dynamics can select for host resistance through increased genetic diversity, recombination and evolutionary rates. However, in haplodiploid organisms such as the honeybee (Apis mellifera), models suggest the selective pressure is weaker than in diploids. Haplodiploid sex determination, found in A.mellifera, can allow deleterious recessive alleles to persist in the population through the diploid sex with negative effects predominantly expressed in the haploid sex. To overcome these negative effects in haploid genomes, epistatic interactions have been hypothesized to play an important role. Here, we use the interaction between A.mellifera and the parasitic mite Varroa destructor to test epistasis in the expression of resistance, through the inhibition of parasite reproduction, in haploid drones. We find novel loci on three chromosomes which explain over 45% of the resistance phenotype. Two of these loci interact only additively, suggesting their expression is independent of each other, but both loci interact epistatically with the third locus. With drone offspring inheriting only one copy of the queen's chromosomes, the drones will only possess one of two queen alleles throughout the years-long lifetime of the honeybee colony. Varroa, in comparison, completes its highly inbred reproductive cycle in a matter of weeks, allowing it to rapidly evolve resistance. Faced with the rapidly evolving Varroa, a diversity of pathways and epistatic interactions for the inhibition of Varroa reproduction could therefore provide a selective advantage to the high levels of recombination seen in A.mellifera. This allows for the remixing of phenotypes despite a fixed queen genotype."
2,1,2,1,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Kathrin Naepflin,2018,https://doi.org/10.1128/JVI.00447-18,"Wang, JY; Shaban, NM; Land, AM; Brown, WL; Harris, RS",Simian Immunodeficiency Virus Vif and Human APOBEC3B Interactions Resemble Those between HIV-1 Vif and Human APOBEC3G,JOURNAL OF VIROLOGY,92,,,UNSP e00447-18,10.1128/JVI.00447-18,"Several members of the APOBEC3 DNA cytosine deaminase family can potently inhibit Vif-deficient human immunodeficiency virus type 1 (HIV-1) by catalyzing cytosine deamination in viral cDNA and impeding reverse transcription. HIV-1 counteracts restriction with the virally encoded Vif protein, which targets relevant APOBEC3 proteins for proteasomal degradation. HIV-1 Vif is optimized for degrading the restrictive human APOBEC3 repertoire, and, in general, lentiviral Vif proteins specifically target the restricting APOBEC3 enzymes of each host species. However, simian immunodeficiency virus SIVmac239 Vif elicits a curiously wide range of APOBEC3 degradation capabilities that include degradation of several human APOBEC3s and even human APOBEC3B, a non-HIV-1-restricting APOBEC3 enzyme. To better understand the molecular determinants of the interaction between SIVmac239 Vif and human APOBEC3B, we analyzed an extensive series of mutants. We found that SIVmac239 Vif interacts with the N-terminal domain of human APOBEC3B and, interestingly, that this occurs within a structural region homologous to the HIV-1 Vif interaction surface of human APOBEC3G. An alanine scan of SIVmac239 Vif revealed several residues required for human APOBEC3B degradation activity. These residues overlap HIV-1 Vif surface residues that interact with human APOBEC3G and are distinct from those that engage APOBEC3F or APOBEC3H. Overall, these studies indicate that the molecular determinants of the functional interaction between human APOBEC3B and SIVmac239 Vif resemble those between human APOBEC3G and HIV-1 Vif. These studies contribute to the growing knowledge of the APOBEC-Vif interaction and may help guide future efforts to disrupt this interaction as an antiviral therapy or exploit the interaction as a novel strategy to inhibit APOBEC3B-dependent tumor evolution. IMPORTANCE Primate APOBEC3 proteins provide innate immunity against retroviruses such as HIV and SIV. HIV-1, the primary cause of AIDS, utilizes its Vif protein to specifically counteract restrictive human APOBEC3 enzymes. SIVmac239 Vif exhibits a much wider range of anti-APOBEC3 activities that includes several rhesus macaque enzymes and extends to multiple proteins in the human APOBEC3 repertoire, including APOBEC3B. Understanding the molecular determinants of the interaction between SIVmac239 Vif and human APOBEC3B adds to existing knowledge on the APOBEC3-Vif interaction and has potential to shed light on what processes may have shaped Vif functionality over evolutionary time. An intimate understanding of this interaction may also lead to a novel cancer therapy because, for instance, creating a derivative of SIVmac239 Vif that specifically targets human APOBEC3B could be used to suppress tumor genomic DNA mutagenesis by this enzyme, slow ongoing tumor evolution, and help prevent poor clinical outcomes."
2,3,3,1,5,within an individuals lifespan (single generation),small spatial scale (couple of populations),single species laboratory system - environmental aspect present,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Kathrin Naepflin,2018,https://doi.org/10.1111/ppa.12834,"Hulin, MT; Mansfield, JW; Brain, P; Xu, X; Jackson, RW; Harrison, RJ",Characterization of the pathogenicity of strains of Pseudomonas syringae towards cherry and plum,PLANT PATHOLOGY,67,1177,1193,,10.1111/ppa.12834,"Bacterial canker is a major disease of Prunus avium (cherry), Prunus domestica (plum) and other stone fruits. It is caused by pathovars within the Pseudomonas syringae species complex including P.syringae pv. morsprunorum (Psm) race 1 (R1), Psm race 2 (R2) and P.syringae pv. syringae (Pss). Psm R1 and Psm R2 were originally designated as the same pathovar; however, phylogenetic analysis revealed them to be distantly related, falling into phylogroups 3 and 1, respectively. This study characterized the pathogenicity of 18 newly genome-sequenced P.syringae strains on cherry and plum, in the field and laboratory. The field experiment confirmed that the cherry cultivar Merton Glory exhibited a broad resistance to all clades. Psm R1 contained strains with differential specificity on cherry and plum. The ability of tractable laboratory-based assays to reproduce assessments on whole trees was examined. Good correlations were achieved with assays using cut shoots or leaves, although only the cut shoot assay was able to reliably discriminate cultivar differences seen in the field. Measuring bacterial multiplication in detached leaves differentiated pathogens from nonpathogens and was therefore suitable for routine testing. In cherry leaves, symptom appearance discriminated Psm races from nonpathogens, which triggered a hypersensitive reaction. Pathogenic strains of Pss rapidly induced disease lesions in all tissues and exhibited a more necrotrophic lifestyle than hemibiotrophic Psm. This in-depth study of pathogenic interactions, identification of host resistance and optimization of laboratory assays provides a framework for future genetic dissection of host-pathogen interactions in the canker disease."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Host,Kathrin Naepflin,2018,https://doi.org/10.1089/cmb.2018.0007,"Boenn, M",ShRangeSim: Simulation of Single Nucleotide Polymorphism Clusters in Next-Generation Sequencing Data,JOURNAL OF COMPUTATIONAL BIOLOGY,25,613,622,,10.1089/cmb.2018.0007,"Genomic variations are in the focus of research to uncover mechanisms of host-pathogen interactions and diseases such as cancer. Nowadays, next-generation sequencing (NGS) data are analyzed through dedicated pipelines to detect them. Surrogate NGS data in conjunction with genomic variations help to evaluate pipelines and validate their outcomes, fostering selection of proper tools for a given scientific question. I describe how existing approaches for simulating NGS data in conjunction with genomic variations fail to model local enrichments of single nucleotide polymorphisms (SNPs), so called SNP clusters. Two distributions for count data are applied to publicly available collections of genomic variations. The results suggest modeling of SNP cluster sizes by overdispersion-aware distributions."
2,1,3,2,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,full gene/regulator,Host,Kathrin Naepflin,2018,https://doi.org/10.3389/fimmu.2018.01206,"Portet, A; Galinier, R; Pinaud, S; Portela, J; Nowacki, F; Gourbal, B; Duval, D",BgTEP: An Antiprotease Involved in Innate Immune Sensing in Biomphalaria glabrata,FRONTIERS IN IMMUNOLOGY,9,,,1206,10.3389/fimmu.2018.01206,"Insect thioester-containing protein (iTEP) is the most recently defined group among the thioester-containing protein (TEP) superfamily. TEPs are key components of the immune system, and iTEPs from flies and mosquitoes were shown to be major immune weapons. Initially characterized from insects, TEP genes homologous to iTEP were further described from several other invertebrates including arthropods, cniderians, and mollusks albeit with few functional characterizations. In the freshwater snail Biomphalaria glabrata, a vector of the schistosomiasis disease, the presence of a TEP protein (BgTEP) was previously described in a well-defined immune complex involving snail lectins (fibrinogen-related proteins) and schistosome parasite mucins (SmPoMuc). To investigate the potential role of BgTEP in the immune response of the snail, we first characterized its genomic organization and its predicted protein structure. A phylogenetic analysis clustered BgTEP in a well-conserved subgroup of mollusk TEP. We then investigated the BgTEP expression profile in different snail tissues and followed immune challenges using different kinds of intruders during infection kinetics. Results revealed that BgTEP is particularly expressed in hemocytes, the immune-specialized cells in invertebrates, and is secreted into the hemolymph. Transcriptomic results further evidenced an intruder-dependent differential expression pattern of BgTEP, while interactome experiments showed that BgTEP is capable of binding to the surface of different microbes and parasite either in its full length form or in processed forms. An immunolocalization approach during snail infection by the Schistosoma mansoni parasite revealed that BgTEP is solely expressed by a subtype of hemocytes, the blast-like cells. This hemocyte subtype is present in the hemocytic capsule surrounding the parasite, suggesting a potential role in the parasite clearance by encapsulation. Through this work, we report the first characterization of a snail TEP. Our study also reveals that BgTEP may display an unexpected functional dual role. In addition to its previously characterized anti-protease activity, we demonstrate that BgTEP can bind to the intruder surface membrane, which supports a likely opsonin role."
1,1,1,1,2,none,no spatial aspect,none - theoretical,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Host,Kathrin Naepflin,2018,https://doi.org/10.1017/S0031182017001159,"Penman, BS; Gupta, S",Detecting signatures of past pathogen selection on human HLA loci: are there needles in the haystack?,PARASITOLOGY,145,731,739,,10.1017/S0031182017001159,"Human leucocyte antigens (HLAs) are responsible for the display of peptide fragments for recognition by T-cell receptors. The gene family encoding them is thus integral to human adaptive immunity, and likely to be under strong pathogen selection. Despite this, it has proved difficult to demonstrate specific examples of pathogen-HLA coevolution. Selection from multiple pathogens simultaneously could explain why the evolutionary signatures of particular pathogens on HLAs have proved elusive. Here, we present an individual-based model of HLA evolution in the presence of two mortality-causing pathogens. We demonstrate that it is likely that individual pathogen species causing high mortality have left recognizable signatures on the HLA genomic region, despite more than one pathogen being present. Such signatures are likely to exist at the whole-population level, and involve haplotypic combinations of HLA genes rather than single loci."
2,3,4,2,5,within an individuals lifespan (single generation),small spatial scale (couple of populations),multiple species laboratory system - no environmental aspect present,full gene/regulator,Pathogen,Kathrin Naepflin,2018,https://doi.org/10.1016/j.virol.2018.01.029,"Laufer, M; Mohammad, H; Maiss, E; Richert-Poggeler, K; Dall'Ara, M; Ratti, C; Gilmer, D; Liebe, S; Varrelmann, M",Biological properties of Beet soil-borne mosaic virus and Beet necrotic yellow vein virus cDNA clones produced by isothermal in vitro recombination: Insights for reassortant appearance,VIROLOGY,518,25,33,,10.1016/j.virol.2018.01.029,"Two members of the Benyviridae family and genus Benyvirus, Beet soil-borne mosaic virus (BSBMV) and Beet necrotic yellow vein virus (BNYVV), possess identical genome organization, host range and high sequence similarity; they infect Beta vulgaris with variable symptom expression. In the US, mixed infections are described with limited information about viral interactions. Vectors suitable for agroinoculation of all genome components of both viruses were constructed by isothermal in vitro recombination. All 35S promoter-driven cDNA clones allowed production of recombinant viruses competent for Nicotiana benthamiana and Beta macrocarpa systemic infection and Polymyxa betae transmission and were compared to available BNYVV B-type clone. BNYVV and BSBMV RNA1 + 2 reassortants were viable and spread long-distance in N. benthamiana with symptoms dependent on the BNYVV type. Small genomic RNAs were exchangeable and systemically infected B. macrocarpa. These infectious clones represent a powerful tool for the identification of specific molecular host-pathogen determinants."
1,3,8,7,4,none,small spatial scale (couple of populations),multiple species in the wild - environment constant,whole genome,Pathogen,Lutz Becks,2018,https://doi.org/10.3389/fgene.2018.00130,"Syme, RA; Martin, A; Wyatt, NA; Lawrence, JA; Muria-Gonzalez, MJ; Friesen, TL; Ellwood, SR",Transposable Element Genomic Fissuring in &ITPyrenophora teres&IT Is Associated With Genome Expansion and Dynamics of Host-Pathogen Genetic Interactions,FRONTIERS IN GENETICS,9,,,130,10.3389/fgene.2018.00130,"Pyrenophora teres, P. teres f. teres (PTT) and P. teres f. maculate (PTM) cause significant diseases in barley, but little is known about the large-scale genomic differences that may distinguish the two forms. Comprehensive genome assemblies were constructed from long DNA reads, optical and genetic maps. As repeat masking in fungal genomes influences the final gene annotations, an accurate and reproducible pipeline was developed to ensure comparability between isolates. The genomes of the two forms are highly collinear, each composed of 12 chromosomes. Genome evolution in P teres is characterized by genome fissuring through the insertion and expansion of transposable elements (TEs), a process that isolates blocks of genic sequence. The phenomenon is particularly pronounced in PTT, which has a larger, more repetitive genome than PTM and more recent transposon activity measured by the frequency and size of genome fissures. PTT has a longer cultivated host association and, notably, a greater range of host-pathogen genetic interactions compared to other Pyrenophora spp., a property which associates better with genome size than pathogen lifestyle. The two forms possess similar complements of TE families with Tc1/Mariner and LINE-like Tad-1 elements more abundant in PTT. Tad-1 was only detectable as vestigial fragments in PTM and, within the forms, differences in genome sizes and the presence and absence of several TE families indicated recent lineage invasions. Gene differences between P. teres forms are mainly associated with gene-sparse regions near or within TE-rich regions, with many genes possessing characteristics of fungal effectors. Instances of gene interruption by transposons resulting in pseudogenization were detected in PTT. In addition, both forms have a large complement of secondary metabolite gene clusters indicating significant capacity to produce an array of different molecules. This study provides genomic resources for functional genetics to help dissect factors underlying the host-pathogen interactions."
1,1,6,7,2,none,no spatial aspect,single species in the wild - environment constant,whole genome,Pathogen,Lutz Becks,2018,https://doi.org/10.1371/journal.pcbi.1006117,"De Maio, N; Worby, CJ; Wilson, DJ; Stoesser, N",Bayesian reconstruction of transmission within outbreaks using genomic variants,PLOS COMPUTATIONAL BIOLOGY,14,,,e1006117,10.1371/journal.pcbi.1006117,"Pathogen genome sequencing can reveal details of transmission histories and is a powerful tool in the fight against infectious disease. In particular, within-host pathogen genomic variants identified through heterozygous nucleotide base calls are a potential source of information to identify linked cases and infer direction and time of transmission. However, using such data effectively to model disease transmission presents a number of challenges, including differentiating genuine variants from those observed due to sequencing error, as well as the specification of a realistic model for within-host pathogen population dynamics. Here we propose a new Bayesian approach to transmission inference, BadTrIP (BAyesian epiDemiological TRansmission Inference from Polymorphisms), that explicitly models evolution of pathogen populations in an outbreak, transmission (including transmission bottlenecks), and sequencing error. BadTrIP enables the inference of host-to-host transmission from pathogen sequencing data and epidemiological data. By assuming that genomic variants are unlinked, our method does not require the computationally intensive and unreliable reconstruction of individual haplotypes. Using simulations we show that BadTrIP is robust in most scenarios and can accurately infer transmission events by efficiently combining information from genetic and epidemiological sources; thanks to its realistic model of pathogen evolution and the inclusion of epidemiological data, BadTrIP is also more accurate than existing approaches. BadTrIP is distributed as an open source package (https://bitbucket.org/nicofmay/badtrip) for the phylogenetic software BEAST2. We apply our method to reconstruct transmission history at the early stages of the 2014 Ebola outbreak, showcasing the power of within-host genomic variants to reconstruct transmission events."
6,5,9,1,11,speciation time (large tree),global spatial scale,multiple species in the wild - environment changing,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Lutz Becks,2018,https://doi.org/10.1111/mec.14558,"Holzer, AS; Bartosova-Sojkova, P; Born-Torrijos, A; Lovy, A; Hartigan, A; Fiala, I",The joint evolution of the Myxozoa and their alternate hosts: A cnidarian recipe for success and vast biodiversity,MOLECULAR ECOLOGY,27,1651,1666,,10.1111/mec.14558,"The relationships between parasites and their hosts are intimate, dynamic and complex; the evolution of one is inevitably linked to the other. Despite multiple origins of parasitism in the Cnidaria, only parasites belonging to the Myxozoa are characterized by a complex life cycle, alternating between fish and invertebrate hosts, as well as by high species diversity. This inspired us to examine the history of adaptive radiations in myxozoans and their hosts by determining the degree of congruence between their phylogenies and by timing the emergence of myxozoan lineages in relation to their hosts. Recent genomic analyses suggested a common origin of Polypodium hydriforme, a cnidarian parasite of acipenseriform fishes, and the Myxozoa, and proposed fish as original hosts for both sister lineages. We demonstrate that the Myxozoa emerged long before fish populated Earth and that phylogenetic congruence with their invertebrate hosts is evident down to the most basal branches of the tree, indicating bryozoans and annelids as original hosts and challenging previous evolutionary hypotheses. We provide evidence that, following invertebrate invasion, fish hosts were acquired multiple times, leading to parallel cospeciation patterns in all major phylogenetic lineages. We identify the acquisition of vertebrate hosts that facilitate alternative transmission and dispersion strategies as reason for the distinct success of the Myxozoa, and identify massive host specification-linked parasite diversification events. The results of this study transform our understanding of the origins and evolution of parasitism in the most basal metazoan parasites known."
6,3,8,1,9,speciation time (large tree),small spatial scale (couple of populations),multiple species in the wild - environment constant,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Lutz Becks,2018,https://doi.org/10.1016/j.virol.2018.01.014,"Gouilh, MA; Puechmaille, SJ; Diancourt, L; Vandenbogaert, M; Serra-Cobo, J; Roig, ML; Brown, P; Moutou, F; Caro, V; Vabret, A; Manuguerra, JC",SARS-CoV related Betacoronavirus and diverse Alphacoronavirus members found in western old-world,VIROLOGY,517,88,97,,10.1016/j.virol.2018.01.014,"The emergence of SARS-CoV and MERS-CoV, triggered the discovery of a high diversity of coronaviruses in bats. Studies from Europe have shown that coronaviruses circulate in bats in France but this reflects only a fraction of the whole diversity. In the current study the diversity of coronaviruses circulating in western Europe was extensively explored. Ten alphacoronaviruses in eleven bat species belonging to the Miniopteridae, Vespertilionidae and Rhinolophidae families and, a SARS-CoV-related Betacoronavirus in Rhinolophus femmequirtum were identified. The diversity and prevalence of bat coronaviruses presently reported from western Europe is much higher than previously described and includes a SARS-CoV sister group. This diversity demonstrates the dynamic evolution and circulation of coronaviruses in this species. That said, the identified coronaviruses were consistently associated with a particular bat species or genus, and these relationships were maintained no matter the geographic location. The observed phylogenetic grouping of coronaviruses from the same species in Europe and Asia, emphasizes the role of host/pathogen coevolution in this group."
1,2,6,7,3,none,local (one population),single species in the wild - environment constant,whole genome,Pathogen,Lutz Becks,2018,https://doi.org/10.1534/g3.117.300429,"Toenshoff, ER; Fields, PD; Bourgeois, YX; Ebert, D","The End of a 60-year Riddle: Identification and Genomic Characterization of an Iridovirus, the Causative Agent of White Fat Cell Disease in Zooplankton",G3-GENES GENOMES GENETICS,8,1259,1272,,10.1534/g3.117.300429,"The planktonic freshwater crustacean of the genus Daphnia are a model system for biomedical research and, in particular, invertebrate-parasite interactions. Up until now, no virus has been characterized for this system. Here we report the discovery of an iridovirus as the causative agent of White Fat Cell Disease (WFCD) in Daphnia. WFCD is a highly virulent disease of Daphnia that can easily be cultured under laboratory conditions. Although it has been studied from sites across Eurasia for more than 60 years, its causative agent had not been described, nor had an iridovirus been connected to WFCD before now. Here we find that an iridovirusthe Daphnia iridescent virus 1 (DIV-1)is the causative agent of WFCD. DIV-1 has a genome sequence of about 288 kbp, with 39% G+C content and encodes 367 predicted open reading frames. DIV-1 clusters together with other invertebrate iridoviruses but has by far the largest genome among all sequenced iridoviruses. Comparative genomics reveal that DIV-1 has apparently recently lost a substantial number of unique genes but has also gained genes by horizontal gene transfer from its crustacean host. DIV-1 represents the first invertebrate iridovirus that encodes proteins to purportedly cap RNA, and it contains unique genes for a DnaJ-like protein, a membrane glycoprotein and protein of the immunoglobulin superfamily, which may mediate host-pathogen interactions and pathogenicity. Our findings end a 60-year search for the causative agent of WFCD and add to our knowledge of iridovirus genomics and invertebrate-virus interactions."
1,1,2,1,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Lutz Becks,2018,https://doi.org/10.1111/mpp.12563,"Kind, S; Schurack, S; Hinsch, J; Tudzynski, P",Brachypodium distachyon as alternative model host system for the ergot fungus Claviceps purpurea,MOLECULAR PLANT PATHOLOGY,19,1005,1011,,10.1111/mpp.12563,"To investigate its susceptibility to ergot infection, we inoculated Brachypodium distachyon with Claviceps purpurea and compared the infection symptoms with those on rye (Secale cereale). We showed that, after inoculation of Brachypodium with Claviceps, the same disease symptoms occurred in comparable temporal and spatial patterns to those on rye. The infection rate of Claviceps on this host was reduced compared with rye, but the disease could be surveyed by fungal genomic DNA quantification. Mutants of Claviceps which were virulence attenuated on rye were also affected on Brachypodium. We were able to show that pathogenesis-related gene expression changed in a typical manner for biotrophic pathogen attack. Our results indicated that the Claviceps-Brachypodium interaction was dependent on salicylic acid, cytokinin and auxin. We consider Brachypodium to be a suitable and useful alternative host; the increased sensitivity compared with rye will be valuable for the identification of infection mechanisms. Future progess in understanding the Claviceps-plant interaction will be facilitated by the use of a well-characterized model host system."
5,1,5,3,6,speciation time (small tree),no spatial aspect,multiple species laboratory system - environmental aspect present,gene family/microsatellites,Pathogen,Lutz Becks,2018,https://doi.org/10.1186/s12862-018-1149-6,"Pereira, SS; Jackson, AP",UDP-glycosyltransferase genes in trypanosomatid genomes have diversified independently to meet the distinct developmental needs of parasite adaptations,BMC EVOLUTIONARY BIOLOGY,18,,,31,10.1186/s12862-018-1149-6,"Background: Trypanosomatid parasites such as Trypanosoma spp. and Leishmania spp. are a major source of infectious disease in humans and domestic animals worldwide. Fundamental to the host-parasite interactions of these potent pathogens are their cell surfaces, which are highly decorated with glycosylated proteins and other macromolecules. Trypanosomatid genomes contain large multi-copy gene families encoding UDP-dependent glycosyltransferases (UGTs), the primary role of which is cell-surface decoration. Here we report a phylogenetic analysis of UGTs from diverse trypanosomatid genomes, the aim of which was to understand the origin and evolution of their diversity. Results: By combining phylogenetics with analyses of recombination, and selection, we compared UGT repertoire, genomic context and sequence evolution across 19 trypanosomatids. We identified a UGT lineage present in stercorarian trypanosomes and a free-living kinetoplastid Bodo saltans that likely represents the ancestral state of this gene family. The phylogeny of parasite-specific genes shows that UGTs repertoire in Leishmaniinae and salivarian trypanosomes has expanded independently and with distinct evolutionary dynamics. In the former, the ancestral UGT repertoire was organised in a tandem array from which sporadic transpositions to telomeric regions occurred, allowing expansion most likely through telomeric exchange. In the latter, the ancestral UGT repertoire was comprised of seven subtelomeric lineages, two of which have greatly expanded potentially by gene transposition between these dynamic regions of the genome. Conclusions: The phylogeny of UGTs confirms that they represent a substantial parasite-specific innovation, which has diversified independently in the distinct trypanosomatid lineages. Nonetheless, developmental regulation has been a strong driver of UGTs diversification in both African trypanosomes and Leishmania."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,both,Lutz Becks,2018,https://doi.org/10.1128/mBio.00473-18,"Low, LY; Harrison, PF; Gould, J; Powell, DR; Choo, JM; Forster, SC; Chapman, R; Gearing, LJ; Cheung, JK; Hertzog, P; Rood, JI",Concurrent Host-Pathogen Transcriptional Responses in a Clostridium perfringens Murine Myonecrosis Infection,MBIO,9,,,e00473-18,10.1128/mBio.00473-18,"To obtain an insight into host-pathogen interactions in clostridial myonecrosis, we carried out comparative transcriptome analysis of both the bacterium and the host in a murine Clostridium perfringens infection model, which is the first time that such an investigation has been conducted. Analysis of the host transcriptome from infected muscle tissues indicated that many genes were upregulated compared to the results seen with mock-infected mice. These genes were enriched for host defense pathways, including Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling components. Real-time PCR confirmed that host TLR2 and NLRP3 inflammasome genes were induced in response to C. perfringens infection. Comparison of the transcriptome of C. perfringens cells from the infected tissues with that from broth cultures showed that host selective pressure induced a global change in C. perfringens gene expression. A total of 33% (923) of C. perfringens genes were differentially regulated, including 10 potential virulence genes that were upregulated relative to their expression in vitro. These genes encoded putative proteins that may be involved in the synthesis of cell wall-associated macromolecules, in adhesion to host cells, or in protection from host cationic antimicrobial peptides. This report presents the first successful expression profiling of coregulated transcriptomes of bacterial and host genes during a clostridial myonecrosis infection and provides new insights into disease pathogenesis and host-pathogen interactions. IMPORTANCE Clostridium perfringens is the causative agent of traumatic clostridial myonecrosis, or gas gangrene. In this study, we carried out transcriptional analysis of both the host and the bacterial pathogen in a mouse myonecrosis infection. The results showed that in comparison to mock-infected control tissues, muscle tissues from C. perfringens-infected mice had a significantly altered gene expression profile. In particular, the expression of many genes involved in the innate immune system was upregulated. Comparison of the expression profiles of C. perfringens cells isolated from the infected tissues with those from equivalent broth cultures identified many potential virulence genes that were significantly upregulated in vivo. These studies have provided a new understanding of the range of factors involved in hostpathogen interactions in a myonecrosis infection."
3,1,6,7,4,few generations,no spatial aspect,single species in the wild - environment constant,whole genome,Pathogen,Lutz Becks,2018,https://doi.org/10.1128/mBio.02125-17,"Pelzek, AJ; Shopsin, B; Radke, EE; Tam, K; Ueberheide, BM; Fenyo, D; Brown, SM; Li, QH; Rubin, A; Fulmer, Y; Chiang, WK; Hernandez, DN; El Bannoudi, H; Sause, WE; Sommerfield, A; Thomsen, IP; Miller, AO; Torres, VJ; Silverman, GJ",Human Memory B Cells Targeting Staphylococcus aureus Exotoxins Are Prevalent with Skin and Soft Tissue Infection,MBIO,9,,,e02125-17,10.1128/mBio.02125-17,"Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S. aureus isolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5%) of patients displayed 2-fold or greater increases in antibody titers against three or more S. aureus antigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range of S. aureus antigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selected S. aureus exotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti-S. aureus memory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses. IMPORTANCE The contribution of B-cell memory and long-term antibody responses to host defenses against S. aureus exotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells against S. aureus secreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory for S. aureus secreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of the S. aureus-host relationship that may better inform strategies for the development of an effective protective vaccine."
5,1,7,7,6,speciation time (small tree),no spatial aspect,single species in the wild - environment changing,whole genome,both,Lutz Becks,2018,https://doi.org/10.1093/molbev/msx304,"Wymant, C; Hall, M; Ratmann, O; Bonsall, D; Golubchik, T; de Cesare, M; Gall, A; Cornelissen, M; Fraser, C",PHYLOSCANNER: Inferring Transmission from Within- and Between-Host Pathogen Genetic Diversity,MOLECULAR BIOLOGY AND EVOLUTION,35,719,733,,10.1093/molbev/msx304,"A central feature of pathogen genomics is that different infectious particles (virions and bacterial cells) within an infected individual may be genetically distinct, with patterns of relatedness among infectious particles being the result of both within-host evolution and transmission from one host to the next. Here, we present a new software tool, phyloscanner, which analyses pathogen diversity from multiple infected hosts. phyloscanner provides unprecedented resolution into the transmission process, allowing inference of the direction of transmission from sequence data alone. Multiply infected individuals are also identified, as they harbor subpopulations of infectious particles that are not connected by within-host evolution, except where recombinant types emerge. Low-level contamination is flagged and removed. We illustrate phyloscanner on both viral and bacterial pathogens, namely HIV-1 sequenced on Illumina and Roche 454 platforms, HCV sequenced with the Oxford Nanopore MinION platform, and Streptococcus pneumoniae with sequences from multiple colonies per individual. phyloscanner is available from https://github.com/BDI-pathogens/phyloscanner."
2,1,8,6,3,within an individuals lifespan (single generation),no spatial aspect,multiple species in the wild - environment constant,exome/transcriptome,Pathogen,Lutz Becks,2018,https://doi.org/10.1007/s00299-017-2244-7,"Ajengui, A; Bertolini, E; Ligorio, A; Chebil, S; Ippolito, A; Sanzani, SM",Comparative transcriptome analysis of two citrus germplasms with contrasting susceptibility to Phytophthora nicotianae provides new insights into tolerance mechanisms,PLANT CELL REPORTS,37,483,499,,10.1007/s00299-017-2244-7,"Host perception of Phytophthora nicotianae switching to necrotrophy is fundamental for disease tolerance of citrus. It involves an HR-like response, strengthening of the cell wall structure and hormonal signaling. Stem rot caused by P. nicotianae is a worldwide disease of several important crops, including citrus. Given the growing awareness of chemical fungicides drawbacks, genetic improvement of citrus rootstocks remains the best alternative. However, the molecular basis underlying the successful response of resistant and/or tolerant genotypes remains poorly understood. Therefore, we performed a transcriptomic analysis to examine the differential defense response to P. nicotianae of two germplasms-tolerant sour orange (SO, Citrus aurantium) and susceptible Madam Vinous (MV, C. sinensis)-in both the biotrophic and necrotrophic phases of host-pathogen interaction. Our results revealed the necrotrophic phase as a decisive turning point, since it included stronger modulation of a number of genes implicated in pathogen perception, signal transduction, HR-like response, transcriptional reprogramming, hormone signaling, and cell wall modifications. In particular, the pathogen perception category reflected the ability of SO to perceive the pathogen even after its switch to necrotrophy, and thus to cope successfully with the infection, while MV failed. The concomitant changes in genes involved in the remaining functional categories seemed to prevent pathogen spread. This investigation provided further understanding of the successful defense mechanisms of C. aurantium against P. nicotianae, which might be exploited in post-genomic strategies to develop resistant Citrus genotypes."
5,3,6,7,8,speciation time (small tree),small spatial scale (couple of populations),single species in the wild - environment constant,whole genome,Pathogen,Lutz Becks,2018,https://doi.org/10.1186/s13073-018-0521-x,"Last, AR; Pickering, H; Roberts, CH; Coll, F; Phelan, J; Burr, SE; Cassama, E; Nabicassa, M; Seth-Smith, HMB; Hadfield, J; Cutcliffe, LT; Clarke, IN; Mabey, DCW; Bailey, RL; Clark, TG; Thomson, NR; Holland, MJ",Population-based analysis of ocular Chlamydia trachomatis in trachoma- endemic West African communities identifies genomic markers of disease severity,GENOME MEDICINE,10,,,15,10.1186/s13073-018-0521-x,"Background: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. Methods: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naive trachoma-endemic population in Guinea-Bissau, West Africa. Results: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043). Conclusions: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Lutz Becks,2018,https://doi.org/10.3389/fcimb.2018.00030,"Marcoleta, AE; Varas, MA; Ortiz-Severin, J; Vasquez, L; Berrios-Pasten, C; Sabag, AV; Chavez, FP; Allende, ML; Santiviago, CA; Monasterio, O; Lagos, R",Evaluating Different Virulence Traits of Klebsiella pneumoniae Using Dictyostelium discoideum and Zebrafish Larvae as Host Models,FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,8,,,30,10.3389/fcimb.2018.00030,"Multiresistant and invasive hypervirulent Klebsiella pneumoniae strains have become one of the most urgent bacterial pathogen threats. Recent analyses revealed a high genomic plasticity of this species, harboring a variety of mobile genetic elements associated with virulent strains, encoding proteins of unknown function whose possible role in pathogenesis have not been addressed. K. pneumoniae virulence has been studied mainly in animal models such as mice and pigs, however, practical, financial, ethical and methodological issues limit the use of mammal hosts. Consequently, the development of simple and cost-effective experimental approaches with alternative host models is needed. In this work we described the use of both, the social amoeba and professional phagocyte Dictyostelium discoideum and the fish Danio rerio (zebrafish) as surrogate host models to study K. pneumoniae virulence. We compared three K. pneumoniae clinical isolates evaluating their resistance to phagocytosis, intracellular survival, lethality, intestinal colonization, and innate immune cells recruitment. Optical transparency of both host models permitted studying the infective process in vivo, following the Klebsiella-host interactions through live-cell imaging. We demonstrated that K. pneumoniae RYC492, but not the multiresistant strains 700603 and BAA-1705, is virulent to both host models and elicits a strong immune response. Moreover, this strain showed a high resistance to phagocytosis by D. discoideum, an increased ability to form biofilms and a more prominent and irregular capsule. Besides, the strain 700603 showed the unique ability to replicate inside amoeba cells. Genomic comparison of the K. pneumoniae strains showed that the RYC492 strain has a higher overall content of virulence factors although no specific genes could be linked to its phagocytosis resistance, nor to the intracellular survival observed for the 700603 strain. Our results indicate that both zebrafish and D. discoideum are advantageous host models to study different traits of K. pneumoniae that are associated with virulence."
5,1,6,7,6,speciation time (small tree),no spatial aspect,single species in the wild - environment constant,whole genome,Pathogen,Lutz Becks,2018,https://doi.org/10.1186/s12864-018-4498-z,"Ruesen, C; Chaidir, L; van Laarhoven, A; Dian, S; Ganiem, AR; Nebenzahl-Guimaraes, H; Huynen, MA; Alisjahbana, B; Dutilh, BE; van Crevel, R",Large-scale genomic analysis shows association between homoplastic genetic variation in Mycobacterium tuberculosis genes and meningeal or pulmonary tuberculosis,BMC GENOMICS,19,,,122,10.1186/s12864-018-4498-z,"Background: Meningitis is the most severe manifestation of tuberculosis. It is largely unknown why some people develop pulmonary TB (PTB) and others TB meningitis (TBM); we examined if the genetic background of infecting M. tuberculosis strains may be relevant. Methods: We whole-genome sequenced M. tuberculosis strains isolated from 322 HIV-negative tuberculosis patients from Indonesia and compared isolates from patients with TBM (n = 106) and PTB (n = 216). Using a phylogeny-adjusted genome-wide association method to count homoplasy events we examined phenotype-related changes at specific loci or genes in parallel branches of the phylogenetic tree. Enrichment scores for the TB phenotype were calculated on single nucleotide polymorphism (SNP), gene, and pathway level. Genetic associations were validated in an independent set of isolates. Results: Strains belonged to the East-Asian lineage (36.0%), Euro-American lineage (61.5%), and Indo-Oceanic lineage (2.5%). We found no association between lineage and phenotype (Chi-square = 4.556; p = 0.207). Large genomic differences were observed between isolates; the minimum pairwise genetic distance varied from 17 to 689 SNPs. Using the phylogenetic tree, based on 28,544 common variable positions, we selected 54 TBM and 54 PTB isolates in terminal branch sets with distinct phenotypes. Genetic variation in Rv0218, and absence of Rv3343c, and nanK were significantly associated with disease phenotype in these terminal branch sets, and confirmed in the validation set of 214 unpaired isolates. Conclusions: Using homoplasy counting we identified genetic variation in three separate genes to be associated with the TB phenotype, including one (Rv0218) which encodes a secreted protein that could play a role in host-pathogen interaction by altering pathogen recognition or acting as virulence effector."
1,3,6,3,4,none,small spatial scale (couple of populations),single species in the wild - environment constant,gene family/microsatellites,Pathogen,Lutz Becks,2018,https://doi.org/10.1534/genetics.117.300481,"MacPherson, A; Otto, SP; Nuismer, SL",Keeping Pace with the Red Queen: Identifying the Genetic Basis of Susceptibility to Infectious Disease,GENETICS,208,779,789,,10.1534/genetics.117.300481,"Genome-wide association studies are widely used to identify disease genes conferring resistance/susceptibility to infectious diseases. Using a combination of mathematical models and simulations, we demonstrate that genetic interactions between hosts and parasites [genotype-by-genotype (G x G) interactions] can drastically affect the results of these association scans and hamper our ability to detect genetic variation in susceptibility. When hosts and parasites coevolve, these G x G interactions often make genome-wide association studies unrepeatable over time or across host populations. Reanalyzing previously published data on Daphnia magna susceptibility to infection by Pasteuria ramosa, we identify genomic regions consistent with G x G interactions. We conclude by outlining possible avenues for designing more powerful and more repeatable association studies."
3,2,7,5,5,few generations,local (one population),single species in the wild - environment changing,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Pathogen,Lutz Becks,2018,https://doi.org/10.1038/s41598-018-20158-x,"Queiros, J; Alves, PC; Vicente, J; Gortazar, C; de la Fuente, J",Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar,SCIENTIFIC REPORTS,8,,,1980,10.1038/s41598-018-20158-x,"Tuberculosis (TB) affects a wide range of host species worldwide. Understanding host-pathogen co-evolution remains a global challenge owing to complex interactions among host genetic factors, pathogen traits and environmental conditions. We used an endemic wild boar population that had undergone a huge increase in Mycobacterium bovis infection prevalence, from 45% in 2002/06 to 83% in 2009/12, to understand the effects of host genetics on host TB outcomes and disease dynamics. Host genomic variation was characterized using a high-density single nucleotide polymorphism (SNP) array, while host TB phenotype was assessed using both gross pathology and mycobacterial culture. Two complementary genome-wide association (GWAS) analyses were conducted: (i) infected-uninfected; and (ii) 2002/06-2009/12. The SNPs with the highest allelic frequency differences between time-periods and TB outcomes were identified and validated in a large dataset. In addition, we quantified the expression levels of some of their closest genes. These analyses highlighted various SNPs (i.e. rs81465339, rs81394585, rs81423166) and some of the closest genes (i.e. LOC102164072, BDNF/NT-3, NTRK2, CDH8, IGSF21) as candidates for host genetic susceptibility. In addition to TB-driven selection, our findings outline the putative role of demographic events in shaping genomic variation in natural populations and how population crashes and drift may impact host genetic susceptibility to TB over time."
2,1,5,6,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - environmental aspect present,exome/transcriptome,Pathogen,Lutz Becks,2018,https://doi.org/10.1186/s12862-018-1123-3,"Krishnan, P; Ma, X; McDonald, BA; Brunner, PC",Widespread signatures of selection for secreted peptidases in a fungal plant pathogen,BMC EVOLUTIONARY BIOLOGY,18,,,7,10.1186/s12862-018-1123-3,"Background: Fungal plant pathogens secrete a large arsenal of hydrolytic enzymes during the course of infection, including peptidases. Secreted peptidases have been extensively studied for their role as effectors. In this study, we combined transcriptomics, comparative genomics and evolutionary analyses to investigate all 39 secreted peptidases in the fungal wheat pathogen Zymoseptoria tritici and its close relatives Z. pseudotritici and Z. ardabiliae. Results: RNA-seq data revealed that a majority of the secreted peptidases displayed differential transcription during the course of Z. tritici infection, indicative of specialization for different stages in the life cycle. Evolutionary analyses detected widespread evidence of adaptive evolution acting on at least 28 of the peptidases. A few peptidases displayed lineage-specific rates of molecular evolution, suggesting altered selection pressure in Z. tritici following host specialization on domesticated wheat. The peptidases belonging to MEROPS families A1 and G1 emerged as a particularly interesting group that may play key roles in host-pathogen co-evolution, host adaptation and pathogenicity. Sister genes in the A1 and G1 families showed accelerated substitution rates after gene duplications. Conclusions: These results suggest widespread evolution of secreted peptidases leading to novel gene functions, consistent with predicted models of ""escape from adaptive conflict"" and ""neo-functionalization"". Our analyses identified candidate genes worthy of functional analyses that may encode effector functions, for example by suppressing plant defenses during the biotrophic phase of infection."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Lutz Becks,2018,https://doi.org/10.1080/20013078.2018.1428004,"Eichenberger, RM; Talukder, MH; Field, MA; Wangchuk, P; Giacomin, P; Loukas, A; Sotillo, J",Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication,JOURNAL OF EXTRACELLULAR VESICLES,7,,,1428004,10.1080/20013078.2018.1428004,"Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where they orchestrate a parasitic existence. Herein we provide the first comprehensive characterization of the excretory/ secretory products of T. muris. We identify 148 proteins secreted by T. muris and show for the first time that the mouse whipworm secretes exosome-like extracellular vesicles (EVs) that can interact with host cells. We use an Optiprep (R) gradient to purify the EVs, highlighting the suitability of this method for purifying EVs secreted by a parasitic nematode. We also characterize the proteomic and genomic content of the EVs, identifying >350 proteins, 56 miRNAs (22 novel) and 475 full-length mRNA transcripts mapping to T. muris gene models. Many of the miRNAs putatively mapped to mouse genes are involved in regulation of inflammation, implying a role in parasite-driven immunomodulation. In addition, for the first time to our knowledge, colonic organoids have been used to demonstrate the internalization of parasite EVs by host cells. Understanding how parasites interact with their host is crucial to develop new control measures. This first characterization of the proteins and EVs secreted by T. muris provides important information on whipworm-host communication and forms the basis for future studies."
2,1,2,1,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Staffan Bensch,2018,https://doi.org/10.2741/4646,"Temeyer, KB",Molecular biology of tick acetylcholinesterases,FRONTIERS IN BIOSCIENCE-LANDMARK,23,1320,1337,,10.2741/4646,"Ticks vector many pathogens with major health and economic impacts and have developed resistance to most acaricides used for tick control Organophosphate (OP) acaricides target acetylcholinesterase (AChE) critical to tick central nervous system function. Mutations producing tick AChEs resistant to OPs were characterized, but tick OP-resistance is not fully elucidated, due to remarkable complexity of tick cholinergic systems. Three paralogous tick AChEs exhibiting differences in primary structure and biochemical kinetics are encoded by amplified genes with developmentally regulated expression. Gene silencing data suggest tick AChEs are functional complements in vivo, and transcriptomic and genomic data suggest existence of additional tick AChEs. Cholinergic systems are crucial in neural transmission and are also regulators of vertebrate immune function Ticks exhibit prolonged intimate host contact, suggesting adaptive functions for tick cholinergic system complexity. AChE was recently reported in tick saliva and a role in manipulation of host immune responses was hypothesized Physiological roles and genetic control of multiple tick AChEs requires further elucidation and may provide unique opportunities to understand and manipulate cholinergic involvement in biological systems."
2,2,9,7,4,within an individuals lifespan (single generation),local (one population),multiple species in the wild - environment changing,whole genome,Pathogen,Staffan Bensch,2018,https://doi.org/10.1093/ve/vey013,"Nelson, CW; Sibley, SD; Kolokotronis, SO; Hamer, GL; Newman, CM; Anderson, TK; Walker, ED; Kitron, UD; Brawn, JD; Ruiz, MO; Goldberg, TL",Selective constraint and adaptive potential of West Nile virus within and among naturally infected avian hosts and mosquito vectors,VIRUS EVOLUTION,4,,,UNSP vey013,10.1093/ve/vey013,"Arthropod-borne viruses are among the most genetically constrained RNA viruses, yet they have a remarkable propensity to adapt and emerge. We studied wild birds and mosquitoes naturally infected with West Nile virus (WNV) in a 'hot spot' of virus transmission in Chicago, IL, USA. We generated full coding WNV genome sequences from spatiotemporally matched bird and mosquito samples using high-throughput sequencing, allowing a molecular evolutionary assessment with deep coverage. Mean F-ST among samples was 0.66 (+/- 0.02 SE) and was bimodal, with mean nucleotide diversity being higher between samples (interhost pi(N) = 0.001; pi(S) = 0.024) than within them (intrahost pi(N) < 0.0001; pi(S) < 0.001). Eight genomic sites with F-ST > 1.01 (in the PrM, NS2a, NS3, NS4b, and 5'-noncoding genomic regions) showed bird versus mosquito variant frequency differences of > 30 per cent and/or polymorphisms fixed in >= 5 host or vector individuals, suggesting host tropism for these variants. However, phylogenetic analyses demonstrated a lack of grouping by bird or mosquito, most inter-sample differences were synonymous (mean interhost pi(N)/pi(S) = 0.04), and there was no significant difference between hosts and vectors in either their nucleotide diversities or levels of purifying selection (mean intrahost pi(N)/pi(S) = 0.28 in birds and pi(N)/pi(S) = 0.21 in mosquitoes). This finding contrasts with the 'trade-off' and 'selective sieve' hypotheses that have been proposed and tested in the laboratory, which predict strong host versus vector effects on WNV genetic variation, with heightened selective constraint in birds alternating with heightened viral diversity in mosquitoes. Overall, our data show WNV to be highly selectively constrained within and between both hosts and vectors but still able to vary at a limited number of sites across the genome. Such site-specific plasticity in the face of overall selective constraint may offer a mechanism whereby highly constrained viruses such as WNV and its relatives can still adapt and emerge."
1,1,3,7,2,none,no spatial aspect,single species laboratory system - environmental aspect present,whole genome,Pathogen,Staffan Bensch,2018,https://doi.org/10.1007/978-1-4939-7383-5_16,"Lin, T; Gao, LH",Genome-Wide Mutagenesis in Borrelia burgdorferi,BORRELIA BURGDORFERI: METHODS AND PROTOCOLS,1690,201,223,,10.1007/978-1-4939-7383-5_16,"Signature-tagged mutagenesis (STM) is a functional genomics approach to identify bacterial virulence determinants and virulence factors by simultaneously screening multiple mutants in a single host animal, and has been utilized extensively for the study of bacterial pathogenesis, host-pathogen interactions, and spirochete and tick biology. The signature-tagged transposon mutagenesis has been developed to investigate virulence determinants and pathogenesis of Borrelia burgdorferi. Mutants in genes important in virulence are identified by negative selection in which the mutants fail to colonize or disseminate in the animal host and tick vector. STM procedure combined with Luminex Flex (R) Map (TM) technology and next-generation sequencing (e.g., Tn-seq) are the powerful high-throughput tools for the determination of Borrelia burgdorferi virulence determinants. The assessment of multiple tissue sites and two DNA resources at two different time points using Luminex Flex (R) Map (TM) technology provides a robust data set. B. burgdorferi transposon mutant screening indicates that a high proportion of genes are the novel virulence determinants that are required for mouse and tick infection. In this protocol, an effective signature-tagged Himar1-based transposon suicide vector was developed and used to generate a sequence-defined library of nearly 4800 mutants in the infectious B. burgdorferi B31 clone. In STM, signature-tagged suicide vectors are constructed by inserting unique DNA sequences (tags) into the transposable elements. The signature-tagged transposon mutants are generated when transposon suicide vectors are transformed into an infectious B. burgdorferi clone, and the transposable element is transposed into the 50-TA-30 sequence in the B. burgdorferi genome with the signature tag. The transposon library is created and consists of many sub-libraries, each sub-library has several hundreds of mutants with same tags. A group of mice or ticks are infected with a mixed population of mutants with different tags, after recovered from different tissues of infected mice and ticks, mutants from output pool and input pool are detected using high-throughput, semi-quantitative Luminex (R) FLEXMAP (TM) or next-generation sequencing (Tn-seq) technologies. Thus far, we have created a high-density, sequence-defined transposon library of over 6600 STM mutants for the efficient genome-wide investigation of genes and gene products required for wild-type pathogenesis, host-pathogen interactions, in vitro growth, in vivo survival, physiology, morphology, chemotaxis, motility, structure, metabolism, gene regulation, plasmid maintenance and replication, etc. The insertion sites of 4480 transposon mutants have been determined. About 800 predicted protein-encoding genes in the genome were disrupted in the STM transposon library. The infectivity and some functions of 800 mutants in 500 genes have been determined. Analysis of these transposon mutants has yielded valuable information regarding the genes and gene products important in the pathogenesis and biology of B. burgdorferi and its tick vectors."
2,1,3,1,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Host,Staffan Bensch,2018,https://doi.org/10.1094/PHYTO-12-16-0448-R,"Fodor, J; Kaman-Toth, E; Danko, T; Schwarczinger, I; Bozso, Z; Pogany, M",Description of the Nicotiana benthamiana-Cercospora nicotianae Pathosystem,PHYTOPATHOLOGY,108,149,155,,10.1094/PHYTO-12-16-0448-R,"Nicotiana benthamiana is a valuable model organism in plant biology research. This report describes its extended applicability in the field of molecular plant pathology by introducing a nonbiotrophic fungal pathogen Cercospora nicotianae that can be conveniently used under laboratory conditions, consistently induces a necrotic leaf spot disease on Nicotiana benthamiana, and is specialized on solanaceous plants. Our inoculation studies showed that C. nicotianae more effectively colonizes N. benthamiana than its conventional host, N. tabacum. The functions of two critical regulators of host immunity, coronatine-insensitive 1 (COI1) and ethylene-insensitive 2 (EIN2), were studied in N. benthamiana using Tobacco rattle virus-based virus-induced gene silencing (VIGS). Perturbation of jasmonic acid or ethylene signaling by VIGS of either COI1 or EIN2, respectively, resulted in markedly increased Cercospora leaf spot symptoms on N. benthamiana plants. These results suggest that the N. benthamiana-C. nicotianae host-pathogen interaction is a prospective but hitherto unutilized pathosystem for studying gene functions in diseased plants."
2,2,6,1,4,within an individuals lifespan (single generation),local (one population),single species in the wild - environment constant,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Staffan Bensch,2018,https://doi.org/10.1016/j.jiph.2017.03.009,"Khademvatan, S; Masjedizadeh, R; Yousefi-Razin, E; Mahbodfar, H; Rahim, F; Yousefi, E; Foroutan, M",PCR-based molecular characterization of Blastocystis hominis subtypes in southwest of Iran,JOURNAL OF INFECTION AND PUBLIC HEALTH,11,43,47,,10.1016/j.jiph.2017.03.009,"Blastocystis hominis is the most common intestinal parasite found in humans and many other hosts. Pathogenicity of Blastocystis sp. remains controversial and it has been suggested that it may be associated with certain subtypes of organism. The aim of this study was to evaluate the molecular epidemiology of B. hominis and its subtype distribution in Ahvaz, southwest of Iran. During 2012-2014, a total of 481 samples were collected from patients referred to the medical laboratory centers in Ahvaz for stool examination. Samples were examined by wet mount, and genomic DNA was extracted from 50 positive samples. PCR was performed using seven primer pairs targeting the SSU rDNA gene and sequenced. 69 (14.35%) samples were found to be positive for B. hominis and the subtypes of 50 samples were identified. Five subtypes (STs) were identified, including: ST1 (22%), ST2 (6%), ST3 (40%), ST4 (2%), and ST5 (8%). 11 (22%) mixed infections were found, of which 5 were a mixture of ST3/ST4. Mixtures of ST1/ST3 and ST1/ST4 were 3, respectively. In this study people infected with ST3 showed the most gastrointestinal symptoms. This is the first study in the population of Ahvaz and indicates the high prevalence of ST3 in this area. The results suggest a possible association between this subtype and pathogenic potential of parasite. (C) 2017 The Authors. Published by Elsevier Limited. This is an open access article under the CC BY-NC-ND license"
1,1,2,1,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Staffan Bensch,2018,https://doi.org/10.1016/j.mimet.2017.11.019,"Vu, TX; Ngo, TT; Mai, LTD; Bui, TT; Le, DH; Bui, HTV; Nguyen, HQ; Ngo, BX; Tran, VT",A highly efficient Agrobacterium tumefaciens-mediated transformation system for the postharvest pathogen Penicillium digitatum using DsRed and GFP to visualize citrus host colonization,JOURNAL OF MICROBIOLOGICAL METHODS,144,134,144,,10.1016/j.mimet.2017.11.019,"Penicillium digitatum is a major postharvest pathogen of citrus crops. This fungus broadly spreads worldwide and causes green mold disease, which results in severe losses for citrus production. Understanding of the citrus infection by P. digitatum may help develop effective strategies for controlling this pathogen. In this study, we have characterized a virulent strain of P. digitatum isolated in Vietnam and established a highly efficient Agrobacterium tumefaciens-mediated transformation (ATMT) system for this fungal strain with two newly constructed binary vectors. These binary vectors harbor dominant selectable markers for hygromycin or nourseothricin resistance, and expression cassettes for the red fluorescent protein (DsRed) or the green fluorescent protein (GFP), respectively. Using the established ATMT system, the transformation efficiency of the Vietnamese strain could reach a very high yield of 1240 +/- 165 transformants per 10(6) spores. Interestingly, we found that GFP is much better than DsRed for in situ visualization of citrus fruit colonization by the fungus. Additionally, we showed that the transformation system can also be used to generate T-DNA insertion mutants for screening nonpathogenic or less virulent strains. Our work provides a new platform including a virulent tropical strain of P. digitatum, an optimized ATMT method and two newly constructed binary vectors for investigation of the postharvest pathogen. This platform will help develop strategies to dissect molecular mechanisms of host-pathogen interactions in more detail as well as to identify potential genes of pathogenicity by either insertional mutagenesis or gene disruption in this important pathogenic fungus."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Staffan Bensch,2018,https://doi.org/10.1534/g3.117.300196,"Wyatt, NA; Richards, JK; Brueggeman, RS; Friesen, TL",Reference Assembly and Annotation of the Pyrenophora teres f. teres Isolate 0-1,G3-GENES GENOMES GENETICS,8,1,8,,10.1534/g3.117.300196,"Pyrenophora teres f. teres, the causal agent of net form net blotch (NFNB) of barley, is a destructive pathogen in barley-growing regions throughout the world. Typical yield losses due to NFNB range from 10 to 40%; however, complete loss has been observed on highly susceptible barley lines where environmental conditions favor the pathogen. Currently, genomic resources for this economically important pathogen are limited to a fragmented draft genome assembly and annotation, with limited RNA support of the P. teres f. teres isolate 0-1. This research presents an updated 0-1 reference assembly facilitated by long-read sequencing and scaffolding with the assistance of genetic linkage maps. Additionally, genome annotation was mediated by RNAseq analysis using three infection time points and a pure culture sample, resulting in 11,541 high-confidence gene models. The 0-1 genome assembly and annotation presented here now contains the majority of the repetitive content of the genome. Analysis of the 0-1 genome revealed classic characteristics of a ""two-speed"" genome, being compartmentalized into GC-equilibrated and AT-rich compartments. The assembly of repetitive AT-rich regions will be important for future investigation of genes known as effectors, which often reside in close proximity to repetitive regions. These effectors are responsible for manipulation of the host defense during infection. This updated P. teres f. teres isolate 0-1 reference genome assembly and annotation provides a robust resource for the examination of the barley-P. teres f. teres host-pathogen coevolution."
1,1,2,1,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Staffan Bensch,2018,https://doi.org/10.1128/IAI.00784-17,"Herrero-Fresno, A; Espinel, IC; Spiegelhauer, MR; Guerra, PR; Andersen, KW; Olsen, JE",The Homolog of the Gene bstA of the BTP1 Phage from Salmonella enterica Serovar Typhimurium ST313 Is an Antivirulence Gene in Salmonella enterica Serovar Dublin,INFECTION AND IMMUNITY,86,,,e00784-17,10.1128/IAI.00784-17,"In a previous study, a novel virulence gene, bstA, identified in a Salmonella enterica serovar Typhimurium sequence type 313 (ST313) strain was found to be conserved in all published Salmonella enterica serovar Dublin genomes. In order to analyze the role of this gene in the host-pathogen interaction in S. Dublin, a mutant where this gene was deleted (S. Dublin Delta bstA) and a mutant which was further genetically complemented with bstA (S. Dublin 3246-C) were constructed and tested in models of in vitro and in vivo infection as well as during growth competition assays in M9 medium, Luria-Bertani broth, and cattle blood. In contrast to the results obtained for a strain of S. Typhimurium ST313, the lack of bstA was found to be associated with increased virulence in S. Dublin. Thus, S. Dublin Delta bstA showed higher levels of uptake than the wild-type strain during infection of mouse and cattle macrophages and higher net replication within human THP-1 cells. Furthermore, during mouse infections, S. Dublin Delta bstA was more virulent than the wild type following a single intraperitoneal infection and showed an increased competitive index during competitive infection assays. Deletion of bstA did not affect either the amount of cytokines released by THP-1 macrophages or the cytotoxicity toward these cells. The histology of the livers and spleens of mice infected with the wild-type strain and the S. Dublin Delta bstA mutant revealed similar levels of inflammation between the two groups. The gene was not important for adherence to or invasion of human epithelial cells and did not influence bacterial growth in rich medium, minimal medium, or cattle blood. In conclusion, a lack of bstA affects the pathogenicity of S. Dublin by decreasing its virulence. Therefore, it might be regarded as an antivirulence gene in this serovar."
4,2,9,7,6,many generations,local (one population),multiple species in the wild - environment changing,whole genome,Pathogen,Staffan Bensch,2018,https://doi.org/10.1038/ismej.2017.157,"Arkhipova, K; Skvortsov, T; Quinn, JP; McGrath, JW; Allen, CCR; Dutilh, BE; McElarney, Y; Kulakov, LA",Temporal dynamics of uncultured viruses: a new dimension in viral diversity,ISME JOURNAL,12,199,211,,10.1038/ismej.2017.157,"Recent work has vastly expanded the known viral genomic sequence space, but the seasonal dynamics of viral populations at the genome level remain unexplored. Here we followed the viral community in a freshwater lake for 1 year using genome-resolved viral metagenomics, combined with detailed analyses of the viral community structure, associated bacterial populations and environmental variables. We reconstructed 8950 complete and partial viral genomes, the majority of which were not persistent in the lake throughout the year, but instead continuously succeeded each other. Temporal analysis of 732 viral genus-level clusters demonstrated that one-fifth were undetectable at specific periods of the year. Based on host predictions for a subset of reconstructed viral genomes, we for the first time reveal three distinct patterns of host-pathogen dynamics, where the viruses may peak before, during or after the peak in their host's abundance, providing new possibilities for modelling of their interactions. Time series metagenomics opens up a new dimension in viral profiling, which is essential to understand the full scale of viral diversity and evolution, and the ecological roles of these important factors in the global ecosystem."
4,1,3,7,5,many generations,no spatial aspect,single species laboratory system - environmental aspect present,whole genome,Pathogen,Staffan Bensch,2017,https://doi.org/10.1016/j.chom.2017.10.010,"De Sordi, L; Khanna, V; Debarbieux, L",The Gut Microbiota Facilitates Drifts in the Genetic Diversity and Infectivity of Bacterial Viruses,CELL HOST & MICROBE,22,801,#ERROR!,,10.1016/j.chom.2017.10.010,"The intestinal microbiota and human health are intimately linked, but interactions between bacteria and bacteriophages in the context of the mammalian intestine remain largely unexplored. We used comparative population genomics to study a tripartite network consisting of a virulent bacteriophage, its bacterial host, and a phage-insensitive bacterial strain both in vitro and within the murine gut. The bacteriophage adapted to infect the insensitive strain when the three partners co-existed in the gut of conventional mice, but not in dixenic mice or in planktonic cultures. The molecular changes associated with modifications in the bacteriophage host spectrum included single amino acid substitutions and an unusual homologous intragenomic recombination event within the genome of the bacteriophage. An intermediate bacterial host isolated from the murine microbiota mediated bacteriophage adaptation. Our data indicate that by offering access to new hosts, the microbiota shifts the genetic diversity of bacteriophages, thereby promoting long-term persistence of bacteriophage populations."
6,5,9,7,11,speciation time (large tree),global spatial scale,multiple species in the wild - environment changing,whole genome,Pathogen,Staffan Bensch,2017,https://doi.org/10.3389/fmicb.2017.02485,"Kiu, R; Caim, S; Alexander, S; Pachori, P; Hall, LJ","Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors",FRONTIERS IN MICROBIOLOGY,8,,,2485,10.3389/fmicb.2017.02485,"Clostridium perfringens is an important cause of animal and human infections, however information about the genetic makeup of this pathogenic bacterium is currently limited. In this study, we sought to understand and characterise the genomic variation, pangenomic diversity, and key virulence traits of 56 C. perfringens strains which included 51 public, and 5 newly sequenced and annotated genomes using Whole Genome Sequencing. Our investigation revealed that C. perfringens has an ""open"" pangenome comprising 11667 genes and 12.6% of core genes, identified as the most divergent single species Gram-positive bacterial pangenome currently reported. Our computational analyses also defined C. perfringens phylogeny (16S rRNA gene) in relation to some 25 Clostridium species, with C. baratii and C. sardiniense determined to be the closest relatives. Profiling virulence -associated factors confirmed presence of well characterised C. perfringens-associated exotoxins genes including-toxin (plc), enterotoxin (cpe), and Perfringolysin 0 (pfo or pfoA), although interestingly there did not appear to be a close correlation with encoded toxin type and disease phenotype. Furthermore, genomic analysis indicated significant horizontal gene transfer events as defined by presence of prophage genomes, and notably absence of CRISPR defence systems in >70% (40/56) of the strains. In relation to antimicrobial resistance mechanisms, tetracycline resistance genes (tet) and anti-defensins genes (mprF) were consistently detected in silico (tet: 75%; mprF: 100%). However, pre-antibiotic era strain genomes did not encode for tet, thus implying antimicrobial selective pressures in C. perfringens evolutionary history over the past 80 years. This study provides new genomic understanding of this genetically divergent multi-host bacterium, and further expands our knowledge on this medically and veterinary important pathogen."
5,1,7,7,6,speciation time (small tree),no spatial aspect,single species in the wild - environment changing,whole genome,Pathogen,Staffan Bensch,2017,https://doi.org/10.3389/fmicb.2017.02389,"Zimpel, CK; Brandao, PE; de Souza, AF; de Souza, RF; Ikuta, CY; Neto, JSF; Camargo, NCS; Heinemann, MB; Guimaraes, AMS",Complete Genome Sequencing of Mycobacterium bovis SP38 and Comparative Genomics of Mycobacterium bovis and M-tuberculosis Strains,FRONTIERS IN MICROBIOLOGY,8,,,2389,10.3389/fmicb.2017.02389,"Mycobacterium bovis causes bovine tuberculosis and is the main organism responsible for zoonotic tuberculosis in humans. We performed the sequencing, assembly and annotation of a Brazilian strain of M. bovis named SP38, and performed comparative genomics of M. bovis genomes deposited in GenBank. M. bovis SP38 has a traditional tuberculous mycobacterium genome of 4,347,648 bp, with 65.5% GC, and 4,216 genes. The majority of CDSs (2,805, 69.3%) have predictive function, while 1,206 (30.07%) are hypothetical. For comparative analysis, 31 M. bovis, 32 M. bovis BCG, and 23 Mycobacterium tuberculosis genomes available in GenBank were selected. M. bovis RDs (regions of difference) and Clonal Complexes (CC) were identified in silico. Genome dynamics of bacterial groups were analyzed by gene orthology and polymorphic sites identification. M. bovis polymorphic sites were used to construct a phylogenetic tree. Our RD analyses resulted in the exclusion of three genomes, mistakenly annotated as virulent M. bovis. M. bovis SP38 along with strain 35 represent the first report of CC European 2 in Brazil, whereas two other M. bovis strains failed to be classified within current CC. Results of M. bovis orthologous genes analysis suggest a process of genome remodeling through genomic decay and gene duplication. Quantification, pairwise comparisons and distribution analyses of polymorphic sites demonstrate greater genetic variability of M. tuberculosis when compared to M. bovis and M. bovis BCG (p = 0.05), indicating that currently defined M. tuberculosis lineages are more genetically diverse than M. bovis CC and animal-adapted MTC (M. tuberculosis Complex) species. As expected, polymorphic sites annotation shows that M. bovis BCG are subjected to different evolutionary pressures when compared to virulent mycobacteria. Lastly, M. bovis phylogeny indicates that polymorphic sites may be used as markers of M. bovis lineages in association with CC. Our findings highlight the need to better understand host-pathogen co-evolution in genetically homogeneous and/or diverse host populations, considering the fact thatM. bovis has a broader host range when compared to M. tuberculosis. Also, the identification of M. bovis genomes not classified within CC indicates that the diversity of M. bovis lineages may be larger than previously thought or that current classification should be reviewed."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Staffan Bensch,2017,https://doi.org/10.1038/s41467-017-02035-9,"Hartmann, BM; Albrecht, RA; Zaslavsky, E; Nudelman, G; Pincas, H; Marjanovic, N; Schotsaert, M; Martinez-Romero, C; Fenutria, R; Ingram, JP; Ramos, I; Fernandez-Sesma, A; Balachandran, S; Garcia-Sastre, A; Sealfon, SC",Pandemic H1N1 influenza A viruses suppress immunogenic RIPK3-driven dendritic cell death,NATURE COMMUNICATIONS,8,,,1931,10.1038/s41467-017-02035-9,"The risk of emerging pandemic influenza A viruses (IAVs) that approach the devastating 1918 strain motivates finding strain-specific host-pathogen mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting cells that activate T cells, linking innate to adaptive immunity. DC infection with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces global RNA degradation. Here, we show that DC infection with seasonal IAV causes immunogenic RIPK3-mediated cell death. Pandemic IAV suppresses this immunogenic DC cell death. Only DC infected with seasonal IAV, but not with pandemic IAV, enhance maturation of uninfected DC and T cell proliferation. In vivo, circulating T cell levels are reduced after pandemic, but not seasonal, IAV infection. Using recombinant viruses, we identify the HA genomic segment as the mediator of cell death inhibition. These results show how pandemic influenza viruses subvert the immune response."
1,3,7,5,4,none,small spatial scale (couple of populations),single species in the wild - environment changing,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Vincenzo Ellis,2017,https://doi.org/10.1111/eva.12514,"Donaldson, ME; Davy, CM; Willis, CKR; McBurney, S; Park, A; Kyle, CJ",Profiling the immunome of little brown myotis provides a yardstick for measuring the genetic response to white-nose syndrome,EVOLUTIONARY APPLICATIONS,10,1076,1090,,10.1111/eva.12514,"White-nose syndrome (WNS) has devastated populations of hibernating bats in eastern North America, leading to emergency conservation listings for several species including the previously ubiquitous little brown myotis (Myotis lucifugus). However, some bat populations near the epicenter of the WNS panzootic appear to be stabilizing after initial precipitous declines, which could reflect a selective immunogenetic sweep. To investigate the hypothesis that WNS exerts significant selection on the immunome of affected bat populations, we developed a novel, high-throughput sequence capture assay targeting 138 adaptive, intrinsic, and innate immunity genes of putative adaptive significance, as well as their respective regulatory regions (similar to 370 kbp of genomic sequence/individual). We used the assay to explore baseline immunogenetic variation in M.lucifugus and to investigate whether particular immune genes/variants are associated with WNS susceptibility. We also used our assay to detect 1,038 putatively neutral single nucleotide polymorphisms and characterize contemporary population structure, providing context for the identification of local immunogenetic adaptation. Sequence capture provided a cost-effective, ""all-in-one"" assay to test for neutral genetic and immunogenetic structure and revealed fine-scale, baseline immunogenetic differentiation between sampling sites <600km apart. We identified functional immunogenetic variants in M.lucifugus associated with WNS susceptibility. This study lays the foundations for future investigations of rangewide immunogenetic adaptation to WNS in M.lucifugus and provides a blueprint for studies of evolutionary rescue in other host-pathogen systems."
1,1,2,3,2,none,no spatial aspect,single species laboratory system - no environmental aspect,gene family/microsatellites,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1007/s12355-017-0512-z,"Scindiya, M; Malathi, P; Kaverinathan, K; Viswanathan, R; Sundar, AR",Molecular Characterization of Pathogenicity Gene Homologs in Colletotrichum falcatum Causing Red Rot in Sugarcane,SUGAR TECH,19,563,572,,10.1007/s12355-017-0512-z,"Variation in Colletotrichum falcatum causing red rot disease of sugarcane is well established at cultural, pathogenic and molecular level. However, limited information is available on genes responsible for pathogen virulence and its pathogenesis. To understand virulence in C. falcatum, detailed studies were taken up using phylogenetically differentiated two isolates viz., Cf671 and Cf92020 vary in their virulence with 28 pathogenicity gene homologs. Important pathogenicity gene homologs amplified were PKS1, SCD1, THR1, Cap5, Cap20, MAF1, Pg1, PG2, Pel1, Pel2, SSD1, APH1, ArpA, ICL1, RGT2, RAC1, CreA, HXT1 and HXT3. Characterization of gene sequences of the selected pathogenicity genes from C. falcatum revealed both intra- and interspecific variation and comparison of genomic sources sequenced among two distinct isolates revealed a definite role of pathogenicity genes in C. falcatum pathogenesis. Differential expression of the pathogenicity gene homologs between isolates has been validated during host pathogen interaction. The present investigation identified the role of pathogenicity genes and their differential expression in C. falcatum pathogenesis for the first time."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1128/mBio.01919-17,"Habig, M; Quade, J; Stukenbrock, EH",Forward Genetics Approach Reveals Host Genotype-Dependent Importance of Accessory Chromosomes in the Fungal Wheat Pathogen Zymoseptoria tritici,MBIO,8,,,e01919-17,10.1128/mBio.01919-17,"The fungal wheat pathogen Zymoseptoria tritici possesses a large complement of accessory chromosomes showing presence/absence polymorphism among isolates. These chromosomes encode hundreds of genes; however, their functional role and why the chromosomes have been maintained over long evolutionary times are so far not known. In this study, we addressed the functional relevance of eight accessory chromosomes in reference isolate IPO323. We induced chromosome losses by inhibiting the beta-tubulin assembly during mitosis using carbendazim and generated several independent isogenic strains, each lacking one of the accessory chromosomes. We confirmed chromosome losses by electrophoretic karyotyping and whole-genome sequencing. To assess the importance of the individual chromosomes during host infection, we performed in planta assays comparing disease development results in wild-type and chromosome mutant strains. Loss of the accessory chromosomes 14, 16, 18, 19, and 21 resulted in increased virulence on wheat cultivar Runal but not on cultivars Obelisk, Titlis, and Riband. Moreover, some accessory chromosomes affected the switch from biotrophy to necrotrophy as strains lacking accessory chromosomes 14, 18, 19, and 21 showed a significantly earlier onset of necrosis than the wild type on the Runal cultivar. In general, we observed that the timing of the lifestyle switch affects the fitness of Z. tritici. Taking the results together, this study was the first to use a forward-genetics approach to demonstrate a cultivar-dependent functional relevance of the accessory chromosomes of Z. tritici during host infection. IMPORTANCE Zymoseptoria tritici is a prominent fungal pathogen of wheat of worldwide distribution. This fungus shows a remarkable genome organization, with a large number of chromosomes that are present in only some isolates and therefore considered to be ""accessory"" chromosomes. To date, the function of these accessory chromosomes in Z. tritici has been unknown, although their maintenance in the species over evolutionary times suggests a functional relevance. Here we deleted whole accessory chromosomes to test the effect of these chromosomes on host specificity and virulence of the fungus. We show for the first time that some accessory chromosomes of Z. tritici affect the fitness of the fungus during host infection in a cultivar-dependent manner. These results show that the accessory chromosomes encode host-specific virulence determinants having a negative effect on fitness. Understanding the population dynamic of the accessory chromosomes and the molecular interaction of pathogen and plant traits is crucial to improve wheat-breeding strategies."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1016/j.fgb.2017.08.008,"Upadhya, R; Lam, WC; Maybruck, BT; Donlin, MJ; Chang, AL; Kayode, S; Ormerod, KL; Fraser, JA; Doering, TL; Lodge, JK",A fluorogenic C. neoformans reporter strain with a robust expression of mcherry expressed from a safe haven site in the genome,FUNGAL GENETICS AND BIOLOGY,108,13,25,,10.1016/j.fgb.2017.08.008,"C. neoformans is an encapsulated fungal pathogen with defined asexual and sexual life cycles. Due to the availability of genetic and molecular tools for its manipulation, it has become a model organism for studies of fungal pathogens, even though it lacks a reliable system for maintaining DNA fragments as extrachromosomal plasmids. To compensate for this deficiency, we identified a genomic gene-free intergenic region where heterologous DNA could be inserted by homologous recombination without adverse effects on the phenotype of the recipient strain. Since such a site in the C. neoformans genome at a different location has been named previously as ""safe haven"", we named this locus second safe haven site (SH2). Insertion of DNA into this site in the genome of the KN99 congenic strain pair caused minimal change in the growth of the engineered strain under a variety of in vitro and in vivo conditions. We exploited this 'safe' locus to create a genetically stable highly fluorescent strain expressing mCherry protein (KN99mCH); this strain closely resembled its wild-type parent (KN99 alpha) in growth under a variety of in vitro stress conditions and in the expression of virulence traits. The efficiency of phagocytosis and the proliferation of KN99mCH inside human monocyte-derived macrophages were comparable to those of KN99a, and the engineered strain showed the expected organ dissemination after inoculation, although there was a slight reduction in virulence. The mCherry fluorescence allowed us to measure specific association of cryptococci with leukocytes in the lungs and mediastinal lymph nodes of infected animals and, for the first-time, to assess their live/dead status in vivo. These results highlight the utility of KN99mCH for elucidation of host-pathogen interactions in vivo. Finally, we generated drug-resistant KN99 strains of both mating types that are marked at the SH2 locus with a specific drug resistant gene cassette; these strains will facilitate the generation of mutant strains by mating."
5,4,8,7,9,speciation time (small tree),species range,multiple species in the wild - environment constant,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.3389/fcimb.2017.00459,"Nourdin-Galindo, G; Sanchez, P; Molina, CF; Espinoza-Rojas, DA; Oliver, C; Ruiz, P; Vargas-Chacoff, L; Carcamo, JG; Figueroa, JE; Mancilla, M; Maracaja-Coutinho, V; Yanez, AJ",Comparative Pan-Genome Analysis of Piscirickettsia salmonis Reveals Genomic Divergences within Genogroups,FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,7,,,459,10.3389/fcimb.2017.00459,"Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis, functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes. Two marked genogroups were identified, as confirmed by phylogenetic and phylogenomic relationships to the LF-89 and EM-90 reference strains, as well as by assessments of genomic structures. Different structural configurations were found for the six identified copies of the ribosomal operon in the P. salmonis genome, indicating translocation throughout the genetic material. Chromosomal divergences in genomic localization and quantity of genetic cassettes were also found for the Dot/Icm type IVB secretion system. To determine divergences between core-genomes, additional pan-genome descriptions were compiled for the so-termed LF and EM genogroups. Open pan-genomes composed of 2,924 and 2,778 genes and core-genomes composed of 2,170 and 2,228 genes were respectively found for the LF and EM genogroups. The core-genomes were functionally annotated using the Gene Ontology, KEGG, and Virulence Factor databases, revealing the presence of several shared groups of genes related to basic function of intracellular survival and bacterial pathogenesis. Additionally, the specific pan-genomes for the LF and EM genogroups were defined, resulting in the identification of 148 and 273 exclusive proteins, respectively. Notably, specific virulence factors linked to adherence, colonization, invasion factors, and endotoxins were established. The obtained data suggest that these genes could be directly associated with inter-genogroup differences in pathogenesis and host-pathogen interactions, information that could be useful in designing novel strategies for diagnosing and controlling P. salmonis infection."
6,2,2,7,8,speciation time (large tree),local (one population),single species laboratory system - no environmental aspect,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1038/s41598-017-13901-3,"Signor, S",Population genomics of Wolbachia and mtDNA in Drosophila simulans from California,SCIENTIFIC REPORTS,7,,,13369,10.1038/s41598-017-13901-3,"Wolbachia pipientis is an intracellular endosymbiont infecting many arthropods and filarial nematodes. Little is known about the short-term evolution of Wolbachia or its interaction with its host. Wolbachia is maternally inherited, resulting in co-inheritance of mitochondrial organelles such as mtDNA. Here I explore the evolution of Wolbachia, and the relationship between Wolbachia and mtDNA, using a large inbred panel of Drosophila simulans. I compare this to the only other large population genomic Wolbachia dataset from D. melanogaster. I find reduced diversity relative to expectation in both Wolbachia and mtDNA, but only mtDNA shows evidence of a recent selective sweep or population bottleneck. I estimate Wolbachia and mtDNA titre in each genotype, and I find considerable variation in both phenotypes, despite low genetic diversity in Wolbachia and mtDNA. A phylogeny of Wolbachia and of mtDNA suggest a recent origin of the infection derived from a single origin. Using Wolbachia and mtDNA titre as a phenotype, I perform the first association analysis using this phenotype with the nuclear genome and find several implicated regions, including one which contains four CAAX-box protein processing genes. CAAX-box protein processing can be an important part of host-pathogen interactions in other systems, suggesting interesting directions for future research."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1186/s12864-017-4163-y,"Kessler, RL; Pavoni, DP; Krieger, MA; Probst, CM",Trypanosoma cruzi specific mRNA amplification by in vitro transcription improves parasite transcriptomics in hostparasite RNA mixtures,BMC GENOMICS,18,,,793,10.1186/s12864-017-4163-y,"Background: Trypanosomatids are a group of protozoan parasites that includes the etiologic agents of important human illnesses as Chagas disease, sleeping sickness and leishmaniasis. These parasites have a significant distinction from other eukaryotes concerning mRNA structure, since all mature mRNAs have an identical species-specific sequence of 39 nucleotides at the 5' extremity, named spliced leader (SL). Considering this peculiar aspect of trypanosomatid mRNA, the aim of the present work was to develop a Trypanosoma cruzi specific in vitro transcription (IVT) linear mRNA amplification method in order to improve parasite transcriptomics analyses. Methods: We designed an oligonucleotide complementary to the last 21 bases of T. cruzi SL sequence, bearing an upstream T7 promoter (T7SL primer), which was used to direct the synthesis of second-strand cDNA. Original mRNA was then amplified by IVT using T7 RNA polymerase. T7SL-amplified RNA from two distinct T. cruzi stages (epimastigotes and trypomastigotes) were deep sequenced in SOLiD platform. Usual poly(A) + RNA and and T7-oligo(dT) amplified RNA (Eberwine method) were also sequenced. RNA-Seq reads were aligned to our new and improved T. cruzi Dm28c genome assembly (PacBio technology) and resulting transcriptome pattern from these three RNA preparation methods were compared, mainly concerning the conservation of mRNA transcritional levels and DEGs detection between epimastigotes and trypomastigotes. Results: T7SL IVT method detected more potential differentially expressed genes in comparison to either poly(A) + RNA or T7dT IVT, and was also able to produce reliable quantifications of the parasite transcriptome down to 3 ng of total RNA. Furthermore, amplification of parasite mRNA in HeLa/epimastigote RNA mixtures showed that T7SL IVT generates transcriptome quantification with similar detection of differentially expressed genes when parasite RNA mass was only 0.1% of the total mixture (R = 0.78 when compared to poly(A) + RNA). Conclusions: The T7SL IVT amplification method presented here allows the detection of more potential parasite differentially expressed genes (in comparison to poly(A) + RNA) in host-parasite mixtures or samples with low amount of RNA. This method is especially useful for trypanosomatid transcriptomics because it produces less bias than PCR-based mRNA amplification. Additionally, by simply changing the complementary region of the T7SL primer, the present method can be applied to any trypanosomatid species."
1,1,2,2,2,none,no spatial aspect,single species laboratory system - no environmental aspect,full gene/regulator,Host,Vincenzo Ellis,2017,https://doi.org/,"Tandon, G; Singh, S; Kaur, S",Comparative analysis of Cf-4 and Cf-19 in tomato (Solanum lycopersicum) - A bioinformatics study,INDIAN JOURNAL OF AGRICULTURAL SCIENCES,87,1365,1370,,,"Tomatoes (Solanum lycopersicum L.), a model fruit crop, are largely affected by leaf mould disease, caused by an Ascomycete (Cladosporium fulvum) leading to significant economic loss across the globe. Though many R genes corresponding to this disease, viz. Cf-2, Cf-4, Cf-5, Cf-6, Cf-9 and Cf-19 are reported but such studies are confined to genomic level rather than proteomic level. Since host parasite interaction occurs at protein level thus in the present study, attempt has been made to carry out the studies of these R genes at proteomic level. Protein sequences of Cf-4 and Cf-19 genes were used for sequence analysis by Conserved Domain Database followed by construction of their three-dimensional models using Modeller. The obtained models were further validated and finalized protein models of both the genes were compared with the help of DALI Server. The present study revealed that there was 89% sequence identity between these proteins whereas they were confined to 78% only at structural level. Model generated from the present study can be used in interaction studies between Cf-4 and Cf-19 and their corresponding avirulence (Avr) protein. Such study would lead to better understanding of genetic basis of susceptibility of the tomato plants to the invading pathogen. This can also help in establishing them as putative candidate gene, which are desirable in development of disease resistant tomato varieties, combating pathogen attack in endeavour of tomato improvement program."
1,1,2,2,2,none,no spatial aspect,single species laboratory system - no environmental aspect,full gene/regulator,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1016/j.bbagrm.2017.08.003,"Govindaraju, G; Jabeena, CA; Sethumadhavan, DV; Rajaram, N; Rajavelu, A",DNA methyltransferase homologue TRDMT1 in Plasmodium falciparum specifically methylates endogenous aspartic acid tRNA,BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS,1860,1047,1057,,10.1016/j.bbagrm.2017.08.003,"In eukaryotes, cytosine methylation regulates diverse biological processes such as gene expression, development and maintenance of genomic integrity. However, cytosine methylation and its functions in pathogenic apicomplexan protozoans remain enigmatic. To address this, here we investigated the presence of cytosine methylation in the nucleic acids of the protozoan Plasmodium falciparurn. Interestingly, P. falciparum has TRDMT1, a conserved homologue of DNA methyltransferase DNMT2. However, we found that TRDMT1 did not methylate DNA, in vitro. We demonstrate that TRDMT1 methylates cytosine in the endogenous aspartic acid tRNA of P. falciparum. Through RNA bisulfite sequencing, we mapped the position of 5-methyl cytosine in aspartic acid tRNA and found methylation only at C38 position. P. faiciparum proteome has significantly higher aspartic acid content and a higher proportion of proteins with poly aspartic acid repeats than other apicomplexan pathogenic protozoans. Proteins with such repeats are functionally important, with significant roles in host-pathogen interactions. Therefore, TRDMT1 mediated C38 methylation of aspartic acid tRNA might play a critical role by translational regulation of important proteins and modulate the pathogenicity of the malarial parasite."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1371/journal.pntd.0006044,"Kokova, DA; Kostidis, S; Morello, J; Dementeva, N; Perina, EA; Ivanov, VV; Ogorodova, LM; Sazonov, AE; Saltykova, IV; Mayboroda, OA",Exploratory metabolomics study of the experimental opisthorchiasis in a laboratory animal model (golden hamster Mesocricetus auratus),PLOS NEGLECTED TROPICAL DISEASES,11,,,e0006044,10.1371/journal.pntd.0006044,"Background Opisthorchiasis is a parasitic infection caused by the liver flukes of the Opisthorchiidae family. Both experimental and epidemiological data strongly support a role of these parasites in the etiology of the hepatobiliary pathologies and an increased risk of intrahepatic cholangiocarcinoma Understanding a functional link between the infection and hepatobiliary pathologies requires a detailed description a host-parasite interaction on different levels of biological regulation including the metabolic response on the infection. The last one, however remains practically undocumented. Here we are describing a host response on Opisthorchildae infection using a metabolomics approach and present the first exploratory metabolomics study of an experimental model of O. felineus infection. Methodology and Principal findings We conducted a Nuclear Magnetic Resonance (NMR) based longitudinal metabolomics study involving a cohort of 30 animals with two degrees of infection and a control group. An exploratory analysis shows that the most noticeable trend (30% of total variance) in the data was related to the gender differences. Therefore further analysis was done of each gender group separately applying a multivariate extension of the ANOVA ASCA (ANOVA simultaneous component analysis). We show that in the males the infection specific time trends are present in the main component (43.5% variance), while in the females it is presented only in the second component and covers 24% of the variance. We have selected and annotated 24 metabolites associated with the observed effects and provided a physiological interpretation of the findings. Conclusions The first exploratory metabolomics study an experimental model of O. felineus infection is presented. Our data show that at early stage of infection a response of an organism unfolds in a gender specific manner. Also main physiological mechanisms affected appear rather nonspecific (a status of the metabolic stress) the data provides a set of the hypothesis for a search of the more specific metabolic markers of the Opisthorchiidae infection. Author summary Opisthorchiasis is a parasitic infection caused by the liver flukes of the Opisthorchiidae family (Trematoda; Platyhelminthes). The liver fluke infections trigger development of the hepatobiliary pathologies such as chronic forms of cholecystitis, cholangitis, pancreatitis, and cholelithiasis. However, the most threatening effect of the Opisthorchiidae infection is an increased risk of intrahepatic cholangiocarcinoma. With this work we are getting an insight into a host response on Opisthorchiidae infection using a metabolomics approach. Metabolomics is a post-genomic discipline studying the metabolome. The dynamic character of the metabolome, its ability to change in response to the external stimuli makes it an optimal ""readout"" for exploratory studies aiming for the description of the systemic responses of an organism. Using this approach we demonstrate that that early response to the O. felineus infection unfolds in a gender-dependent manner. Moreover, with this first exploratory analysis of the metabolic response to O. felineus infection in an animal model we present a subset of the metabolites changing during the early phase of the infection and offer a possible physiological interpretation."
1,1,2,1,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1128/JVI.01289-17,"Liu, J; Cattadori, IM; Sim, DG; Eden, JS; Holmes, EC; Read, AF; Kerr, PJ",Reverse Engineering Field Isolates of Myxoma Virus Demonstrates that Some Gene Disruptions or Losses of Function Do Not Explain Virulence Changes Observed in the Field,JOURNAL OF VIROLOGY,91,,,UNSP e01289-17,10.1128/JVI.01289-17,"The coevolution of myxoma virus (MYXV) and wild European rabbits in Australia and Europe is a paradigm for the evolution of a pathogen in a new host species. Genomic analyses have identified the mutations that have characterized this evolutionary process, but defining causal mutations in the pathways from virulence to attenuation and back to virulence has not been possible. Using reverse genetics, we examined the roles of six selected mutations found in Australian field isolates of MYXV that fall in known or potential virulence genes. Several of these mutations occurred in genes previously identified as virulence genes in whole-gene knockout studies. Strikingly, no single or double mutation among the mutations tested had an appreciable impact on virulence. This suggests either that virulence evolution was defined by amino acid changes other than those analyzed here or that combinations of multiple mutations, possibly involving epistatic interactions or noncoding sequences, have been critical in the ongoing evolution of MYXV virulence. In sum, our results show that single-gene knockout studies of a progenitor virus can have little power to predict the impact of individual mutations seen in the field. The genetic determinants responsible for this canonical case of virulence evolution remain to be determined. IMPORTANCE The species jump of myxoma virus (MYXV) from the South American tapeti to the European rabbit populations of Australia and Europe is a canonical example of host-pathogen coevolution. Detailed molecular studies have identified multiple genes in MYXV that are critical for virulence, and genome sequencing has revealed the evolutionary history of MYXV in Australia and Europe. However, it has not been possible to categorically identify the key mutations responsible for the attenuation of or reversion to virulence during this evolutionary process. Here we use reverse genetics to examine the role of mutations in viruses isolated early and late in the Australian radiation of MYXV. Surprisingly, none of the candidate mutations that we identified as likely having roles in attenuation proved to be important for virulence. This indicates that considerable caution is warranted when interpreting the possible role of individual mutations during virulence evolution."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.3389/fcimb.2017.00412,"Wang, S; Zhu, XQ; Cai, XP",Gene Duplication Analysis Reveals No Ancient Whole Genome Duplication but Extensive Small-Scale Duplications during Genome Evolution and Adaptation of Schistosoma mansoni,FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,7,,,412,10.3389/fcimb.2017.00412,"Gene duplication (GD), thought to facilitate evolutionary innovation and adaptation, has been studied in many phylogenetic lineages. However, it remains poorly investigated in trematodes, a medically important parasite group that has been evolutionarily specialized during long-term host-parasite interaction. In this study, we conducted a genome-wide study of GD modes and contributions in Schistosoma mansoni, a pathogen causing human schistosomiasis. We combined several lines of evidence provided by duplicate age distributions, genomic sequence similarity, depth-of-coverage and gene synteny to identify the dominant drivers that contribute to the origins of new genes in this parasite. The gene divergences following duplication events (gene structure, expression and function retention) were also analyzed. Our results reveal that the genome lacks whole genome duplication (WGD) in a long evolutionary time and has few large segmental duplications, but is extensively shaped by the continuous small-scale gene duplications (SSGDs) (i.e., dispersed, tandem and proximal GDs) that may be derived from (retro-) transposition and unequal crossing over. Additionally, our study shows that the genes generated by tandem duplications have the smallest divergence during the evolution. Finally, we demonstrate that SSGDs, especially the tandem duplications, greatly contribute to the expansions of some preferentially retained pathogenesis-associated gene families that are associated with the parasite's survival during infection. This study is the first to systematically summarize the landscape of GDs in trematodes and provides new insights of adaptations to parasitism linked to GD events for these parasites."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1099/mgen.0.000122,"Robinson, KM; Hawkins, AS; Santana-Cruz, I; Adkins, RS; Shetty, AC; Nagaraj, S; Sadzewicz, L; Tallon, LJ; Rasko, DA; Fraser, CM; Mahurkar, A; Silva, JC; Hotopp, JCD",Aligner optimization increases accuracy and decreases compute times in multi-species sequence data,MICROBIAL GENOMICS,3,,,122,10.1099/mgen.0.000122,"As sequencing technologies have evolved, the tools to analyze these sequences have made similar advances. However, for multi-species samples, we observed important and adverse differences in alignment specificity and computation time for BWA-MEM (Burrows-Wheeler aligner-maximum exact matches) relative to BWA-ALN. Therefore, we sought to optimize BWA-MEM for alignment of data from multi-species samples in order to reduce alignment time and increase the specificity of alignments. In the multi-species cases examined, there was one majority member (i.e. Plasmodium falciparum or Brugia malayi) and one minority member (i.e. human or the Wolbachia endosymbiont wBm) of the sequence data. Increasing BWA-MEM seed length from the default value reduced the number of read pairs from the majority sequence member that incorrectly aligned to the reference genome of the minority sequence member. Combining both source genomes into a single reference genome increased the specificity of mapping, while also reducing the central processing unit (CPU) time. In Plasmodium, at a seed length of 18 nt, 24.1% of reads mapped to the human genome using 1.7 +/- 0.1 CPU hours, while 83.6% of reads mapped to the Plasmodium genome using 0.2 +/- 0.0 CPU hours (total: 107.7% reads mapping; in 1.9 +/- 0.1 CPU hours). In contrast, 97.1% of the reads mapped to a combined Plasmodium-human reference in only 0.7 +/- 0.0 CPU hours. Overall, the results suggest that combining all references into a single reference database and using a 23 nt seed length reduces the computational time, while maximizing specificity. Similar results were found for simulated sequence reads from a mock metagenomic data set. We found similar improvements to computation time in a publicly available human-only data set."
5,1,5,7,6,speciation time (small tree),no spatial aspect,multiple species laboratory system - environmental aspect present,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1128/mSphere.00213-17,"Antic, I; Brothers, KM; Stolzer, M; Lai, H; Powell, E; Eutsey, R; Cuevas, RA; Miao, XY; Kowalski, RP; Shanks, RMQ; Durand, D; Hiller, NL",Gene Acquisition by a Distinct Phyletic Group within Streptococcus pneumoniae Promotes Adhesion to the Ocular Epithelium,MSPHERE,2,,,e00213-17,10.1128/mSphere.00213-17,"Streptococcus pneumoniae (pneumococcus) displays broad tissue tropism and infects multiple body sites in the human host. However, infections of the conjunctiva are limited to strains within a distinct phyletic group with multilocus sequence types ST448, ST344, ST1186, ST1270, and ST2315. In this study, we sequenced the genomes of six pneumococcal strains isolated from eye infections. The conjunctivitis isolates are grouped in a distinct phyletic group together with a subset of nasopharyngeal isolates. The keratitis (infection of the cornea) and endophthalmitis (infection of the vitreous body) isolates are grouped with the remainder of pneumococcal strains. Phenotypic characterization is consistent with morphological differences associated with the distinct phyletic group. Specifically, isolates from the distinct phyletic group form aggregates in planktonic cultures and chain-like structures in biofilms grown on abiotic surfaces. To begin to investigate the association between genotype and epidemiology, we focused on a predicted surface-exposed adhesin (SspB) encoded exclusively by this distinct phyletic group. Phylogenetic analysis of the gene encoding SspB in the context of a streptococcal species tree suggests that sspB was acquired by lateral gene transfer from Streptococcus suis. Furthermore, an sspB deletion mutant displays decreased adherence to cultured cells from the ocular epithelium compared to the isogenic wild-type and complemented strains. Together these findings suggest that acquisition of genes from outside the species has contributed to pneumococcal tissue tropism by enhancing the ability of a subset of strains to infect the ocular epithelium causing conjunctivitis. IMPORTANCE Changes in the gene content of pathogens can modify their ability to colonize and/or survive in different body sites in the human host. In this study, we investigate a gene acquisition event and its role in the pathogenesis of Streptococccus pneumoniae (pneumococcus). Our findings suggest that the gene encoding the predicted surface protein SspB has been transferred from Streptococcus suis (a distantly related streptococcal species) into a distinct set of pneumococcal strains. This group of strains distinguishes itself from the remainder of pneumococcal strains by extensive differences in genomic composition and by the ability to cause conjunctivitis. We find that the presence of sspB increases adherence of pneumococcus to the ocular epithelium. Thus, our data support the hypothesis that a subset of pneumococcal strains has gained genes from neighboring species that enhance their ability to colonize the epithelium of the eye, thus expanding into a new niche."
5,1,2,7,6,speciation time (small tree),no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1128/mBio.01283-17,"Benjak, A; Honap, TP; Avanzi, C; Becerril-Villanueva, E; Estrada-Garcia, I; Rojas-Espinosa, O; Stone, AC; Cole, ST",Insights from the Genome Sequence of Mycobacterium lepraemurium: Massive Gene Decay and Reductive Evolution,MBIO,8,,,e01283-17,10.1128/mBio.01283-17,"Mycobacterium lepraemurium is the causative agent of murine leprosy, a chronic, granulomatous disease similar to human leprosy. Due to the similar clinical manifestations of human and murine leprosy and the difficulty of growing both bacilli axenically, Mycobacterium leprae and M. lepraemurium were once thought to be closely related, although it was later suggested that M. lepraemurium might be related to Mycobacterium avium. In this study, the complete genome of M. lepraemurium was sequenced using a combination of PacBio and Illumina sequencing. Phylogenomic analyses confirmed that M. lepraemurium is a distinct species within the M. avium complex (MAC). The M. lepraemurium genome is 4.05 Mb in length, which is considerably smaller than other MAC genomes, and it comprises 2,682 functional genes and 1,139 pseudogenes, which indicates that M. lepraemurium has undergone genome reduction. An error-prone repair homologue of the DNA polymerase III alpha-subunit was found to be nonfunctional in M. lepraemurium, which might contribute to pseudogene formation due to the accumulation of mutations in nonessential genes. M. lepraemurium has retained the functionality of several genes thought to influence virulence among members of the MAC. IMPORTANCE Mycobacterium lepraemurium seems to be evolving toward a minimal set of genes required for an obligatory intracellular lifestyle within its host, a niche seldom adopted by most mycobacteria, as they are free-living. M. lepraemurium could be used as a model to elucidate functions of genes shared with other members of the MAC. Its reduced gene set can be exploited for studying the essentiality of genes in related pathogenic species, which might lead to discovery of common virulence factors or clarify host-pathogen interactions. M. lepraemurium can be cultivated in vitro only under specific conditions and even then with difficulty. Elucidating the metabolic (in) capabilities of M. lepraemurium will help develop suitable axenic media and facilitate genetic studies."
2,1,3,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,Host,Vincenzo Ellis,2017,https://doi.org/10.1002/ece3.3234,"Davy, CM; Donaldson, ME; Willis, CKR; Saville, BJ; McGuire, LP; Mayberry, H; Wilcox, A; Wibbelt, G; Misra, V; Bollinger, T; Kyle, CJ",The other white-nose syndrome transcriptome: Tolerant and susceptible hosts respond differently to the pathogen Pseudogymnoascus destructans,ECOLOGY AND EVOLUTION,7,7161,7170,,10.1002/ece3.3234,"Mitigation of emerging infectious diseases that threaten global biodiversity requires an understanding of critical host and pathogen responses to infection. For multihost pathogens where pathogen virulence or host susceptibility is variable, host-pathogen interactions in tolerant species may identify potential avenues for adaptive evolution in recently exposed, susceptible hosts. For example, the fungus Pseudogymnoascus destructans causes white-nose syndrome (WNS) in hibernating bats and is responsible for catastrophic declines in some species in North America, where it was recently introduced. Bats in Europe and Asia, where the pathogen is endemic, are only mildly affected. Different environmental conditions among Nearctic and Palearctic hibernacula have been proposed as an explanation for variable disease outcomes, but this hypothesis has not been experimentally tested. We report the first controlled, experimental investigation of response to P.destructans in a tolerant, European species of bat (the greater mouse-eared bat, Myotis myotis). We compared body condition, disease outcomes and gene expression in control (sham-exposed) and exposed M.myotis that hibernated under controlled environmental conditions following treatment. Tolerant M.myotis experienced extremely limited fungal growth and did not exhibit symptoms of WNS. However, we detected no differential expression of genes associated with immune response in exposed bats, indicating that immune response does not drive tolerance of P.destructans in late hibernation. Variable responses to P.destructans among bat species cannot be attributed solely to environmental or ecological factors. Instead, our results implicate coevolution with the pathogen, and highlight the dynamic nature of the white-nose syndrome transcriptome. Interspecific variation in response to exposure by the host (and possibly pathogen) emphasizes the importance of context in studies of the bat-WNS system, and robust characterization of genetic responses to exposure in various hosts and the pathogen should precede any attempts to use particular bat species as generalizable model hosts."""
2,2,6,5,4,within an individuals lifespan (single generation),local (one population),single species in the wild - environment constant,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Vincenzo Ellis,2017,https://doi.org/10.1111/mec.14228,"Schwensow, NI; Detering, H; Pederson, S; Mazzoni, C; Sinclair, R; Peacock, D; Kovaliski, J; Cooke, B; Fickel, J; Sommer, S",Resistance to RHD virus in wild Australian rabbits: Comparison of susceptible and resistant individuals using a genomewide approach,MOLECULAR ECOLOGY,26,4551,4561,,10.1111/mec.14228,"Deciphering the genes involved in disease resistance is essential if we are to understand host-pathogen coevolutionary processes. The rabbit haemorrhagic disease virus (RHDV) was imported into Australia in 1995 as a biocontrol agent to manage one of the most successful and devastating invasive species, the European rabbit (Oryctolagus cuniculus). During the first outbreaks of the disease, RHDV caused mortality rates of up to 97%. Recently, however, increased genetic resistance to RHDV has been reported. Here, we have aimed to identify genomic differences between rabbits that survived a natural infection with RHDV and those that died in the field using a genomewide next-generation sequencing (NGS) approach. We detected 72 SNPs corresponding to 133 genes associated with survival of a RHD infection. Most of the identified genes have known functions in virus infections and replication, immune responses or apoptosis, or have previously been found to be regulated during RHD. Some of the genes identified in experimental studies, however, did not seem to play a role under natural selection regimes, highlighting the importance of field studies to complement the genomic background of wildlife diseases. Our study provides a set of candidate markers as a tool for the future scanning of wild rabbits for their resistance to RHDV. This is important both for wild rabbit populations in southern Europe where RHD is regarded as a serious problem decimating the prey of endangered predator species and for assessing the success of currently planned RHDV variant biocontrol releases in Australia."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1017/S0031182017000348,"Thompson, PC; Zarlenga, DS; Liu, MY; Rosenthal, BM","Long-read sequencing improves assembly of Trichinella genomes 10-fold, revealing substantial synteny between lineages diverged over 7 million years",PARASITOLOGY,144,1302,1315,,10.1017/S0031182017000348,"Genome assemblies can form the basis of comparative analyses fostering insight into the evolutionary genetics of a parasite's pathogenicity, host-pathogen interactions, environmental constraints and invasion biology; however, the length and complexity of many parasite genomes has hampered the development of well-resolved assemblies. In order to improve Trichinella genome assemblies, the genome of the sylvatic encapsulated species Trichinella murrelli was sequenced using third-generation, long-read technology and, using syntenic comparisons, scaffolded to a reference genome assembly of Trichinella spiralis, markedly improving both. A high-quality draft assembly for T. murrelli was achieved that totalled 63.2 Mbp, half of which was condensed into 26 contigs each longer than 571 000 bp. When compared with previous assemblies for parasites in the genus, ours required 10-fold fewer contigs, which were five times longer, on average. Better assembly across repetitive regions also enabled resolution of 8 Mbp of previously indeterminate sequence. Furthermore, syntenic comparisons identified widespread scaffold misassemblies in the T. spiralis reference genome. The two new assemblies, organized for the first time into three chromosomal scaffolds, will be valuable resources for future studies linking phenotypic traits within each species to their underlying genetic bases."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Pathogen,Vincenzo Ellis,2017,https://doi.org/10.1016/j.ijpara.2017.01.007,"Cuesta-Astroz, Y; de Oliveira, FS; Nahum, LA; Oliveira, G",Helminth secretomes reflect different lifestyles and parasitized hosts,INTERNATIONAL JOURNAL FOR PARASITOLOGY,47,529,544,,10.1016/j.ijpara.2017.01.007,"Helminths cause a number of medical and agricultural problems and are a major cause of parasitic infections in humans, animals and plants. Comparative analysis of helminth genes and genomes are important to understand the genomic biodiversity and evolution of parasites and their hosts in terms of different selective pressures in their habitats. The interactions between the infective organisms and their hosts are mediated in large part by secreted proteins, known collectively as the ""secretome"". Proteins secreted by parasites are able to modify a host's environment and modulate their immune system. The composition and function of this set of proteins varies depending on the ecology, lifestyle and environment of an organism. The present study aimed to predict, in silico, the secretome in 44 helminth species including Nematoda (31 species) and Platyhelminthes (13 species) and, understand the diversity and evolution of secretomes. Secretomes from plant helminths range from 7.6% (943 proteins) to 13.9% (2,077 proteins) of the filtered proteome with an average of 10.2% (1,412 proteins) and from free-living helminths range from 4.4% (870 proteins) to 13% (3,121 proteins) with an average of 9.8% (2,126 proteins), respectively, and thus are considerably larger secretomes in relation to animal helminth secretomes which range from 4.2% (431 proteins) to 11.8% (2,419 proteins) of the proteomes, with an average of 7.1% (804 proteins). Across 44 secretomes in different helminth species, we found five conserved domains: (i) PF00014 (Kunitz/Bovine pancreatic trypsin inhibitor domain), (ii) PF00046 (Homeobox domain), (iii) PF00188 (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins), (iv) PF00085 (Thioredoxin) and (v) PF07679 (Immunoglobulin I-set domain). Our results detected secreted proteins associated with invasion, infection, adhesion and immunoregulation processes as protease inhibitors and cytokines, among other functions. In summary, this study will contribute towards the understanding of host-parasite interactions and possibly identify new molecular targets for the treatment or diagnosis of helminthiases. (C) 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Vincenzo Ellis,2017,https://doi.org/10.3389/fmicb.2017.01421,"Xu, J; Xu, XX; Shakeel, M; Li, SZ; Wang, S; Zhou, XQ; Yu, JL; Xu, XJ; Yu, XQ; Jin, FL",The Entomopathogenic Fungi Isaria fumosorosea Plays a Vital Role in Suppressing the Immune System of Plutella xylostella: RNA-Seq and DGE Analysis of Immunity-Related Genes,FRONTIERS IN MICROBIOLOGY,8,1,14,1421,10.3389/fmicb.2017.01421,"Most, if not all, entomopathogenic fungi have been used as alternative control agents to decrease the insect resistance and harmful effects of the insecticides on the environment. Among them, Isaria fumosorosea has also shown great potential to control different insect pests. In the present study, we explored the immune response of P. xylostella to the infection of I, fumosorosea at different time points by using RNA-Sequencing and differential gene expression technology at the genomic level. To gain insight into the host-pathogen interaction at the genomic level, five libraries of P xylostella larvae at 12, 18, 24, and 36 h post-infection and a control were constructed. In total, 161 immunity related genes were identified and grouped into four categories: immune recognition families, toll and Imd pathway, melanization, and antimicrobial peptides (AMPs). The results of differentially expressed immunity-related genes depicted that 15, 13, 53, and 14 up regulated and 38, 51, 56, and 49 were down-regulated in P. xylostella at 12, 18, 24, and 36 h post-treatment, respectively. RNA-Seq results of immunity-related genes revealed that the expression of AMPs was reduced after treatment with I. fumosorosea. To validate RNA-Seq results by RT-qPCR, 22 immunity-related genes were randomly selected. In conclusion, our results demonstrate that I. fumosorosea has the potential to suppress the immune response of P. xylostella and can become a potential biopesticide for controlling P. xylostella."
4,3,6,7,7,many generations,small spatial scale (couple of populations),single species in the wild - environment constant,whole genome,both,Nina Hafer,2017,https://doi.org/10.1038/s41467-017-00158-7,"Laanto, E; Hoikkala, V; Ravantti, J; Sundberg, LR",Long-term genomic coevolution of host-parasite interaction in the natural environment,NATURE COMMUNICATIONS,8,,,111,10.1038/s41467-017-00158-7,"Antagonistic coevolution of parasite infectivity and host resistance may alter the biological functionality of species, yet these dynamics in nature are still poorly understood. Here we show the molecular details of a long-term phage-bacterium arms race in the environment. Bacteria (Flavobacterium columnare) are generally resistant to phages from the past and susceptible to phages isolated in years after bacterial isolation. Bacterial resistance selects for increased phage infectivity and host range, which is also associated with expansion of phage genome size. We identified two CRISPR loci in the bacterial host: a type II-C locus and a type VI-B locus. While maintaining a core set of conserved spacers, phage-matching spacers appear in the variable ends of both loci over time. The spacers mostly target the terminal end of the phage genomes, which also exhibit the most variation across time, resulting in arms-race-like changes in the protospacers of the coevolving phage population."
5,3,8,2,8,speciation time (small tree),small spatial scale (couple of populations),multiple species in the wild - environment constant,full gene/regulator,Pathogen,Nina Hafer,2017,https://doi.org/,"Cruz, J; Tenreiro, R; Cruz, L",ASSESSMENT OF DIVERSITY OF XANTHOMONAS CAMPESTRIS PATHOVARS AFFECTING CRUCIFEROUS PLANTS IN PORTUGAL AND DISCLOSURE OF TWO NOVEL X-CAMPESTRIS pv. CAMPESTRIS RACES,JOURNAL OF PLANT PATHOLOGY,99,403,414,,,"Xanthomonas campestris includes pathovars X. campestris pv. campestris, X. campestris pv. raphani and X. campestris pv. incanae, causing distinct diseases in Brassicaceae crops, ornamentals and weeds as well as on some Solanaceae crops. In Portugal, where brassica crops production has great economic importance, the presence of the first two pathovars was established. A polyphasic approach combining phenotypic, phylogenetic and genomic data was used to identify and characterize a set of 33 X. campestris isolates collected in Portugal. Pathogenicity tests on a wide host range demonstrated the presence of pathovar X. campestris pv. incanae for the first time in the country. Among X. campestris pv. campestris isolates, presence of races 4, 6 and 7 was recorded and two novel races of this pathovar, race 10 and race 11, were described. Phylogenetic relationships using gyrB gene confirmed phenotypic identification at species level and grouped X. campestris isolates in clades mostly congruent with pathovar allocation. PCR fingerprinting allowed discrimination at strain level of isolates collected from the same host species in the same year and county and revealed high levels of intra-pathovar and intra-race genomic diversity amongst Portuguese X. campestris pv. campestris isolates. Screening of eight essential virulence genes established five different partial virulence profiles, being the full set of genes present in the majority of isolates. When genomic clustering, phylogenetic positioning and virulence profiles were compared, no evident associations with race, host and county of origin were found, confirming the high levels of diversity of X. campestris pathovars in Portugal."
1,1,2,3,2,none,no spatial aspect,single species laboratory system - no environmental aspect,gene family/microsatellites,Pathogen,Nina Hafer,2017,https://doi.org/10.1128/mBio.00756-17,"Hancz, D; Westerlund, E; Bastiat-Sempe, B; Sharma, O; Valfridsson, C; Meyer, L; Love, JF; O'Seaghdha, M; Wessels, MR; Persson, JJ",Inhibition of Inflammasome-Dependent Interleukin 1 beta Production by Streptococcal NAD(+)-Glycohydrolase: Evidence for Extracellular Activity,MBIO,8,,,e00756-17,10.1128/mBio.00756-17,"Group A Streptococcus (GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD(+)-glycohydrolase (NADase). Overexpression of these toxins has been linked to increased bacterial virulence and is correlated with invasive GAS disease. NADase can be translocated into host cells by a SLO-dependent mechanism, and cytosolic NADase has been assigned multiple properties such as protection of intracellularly located GAS bacteria and induction of host cell death through energy depletion. Here, we used a set of isogenic GAS mutants and a macrophage infection model and report that streptococcal NADase inhibits the innate immune response by decreasing inflammasome-dependent interleukin 1 beta (IL-1 beta) release from infected macrophages. Regulation of IL-1 beta was independent of phagocytosis and ensued also under conditions not allowing SLO-dependent translocation of NADase into the host cell cytosol. Thus, our data indicate that NADase not only acts intracellularly but also has an immune regulatory function in the extracellular niche. IMPORTANCE In the mid-1980s, the incidence and severity of invasive infections caused by serotype M1 GAS suddenly increased. The results of genomic analyses suggested that this increase was due to the spread of clonal bacterial strains and identified a recombination event leading to enhanced production of the SLO and NADase toxins in these strains. However, despite its apparent importance in GAS pathogenesis, the function of NADase remains poorly understood. In this study, we demonstrate that NADase inhibits inflammasome-dependent IL-1 beta release from infected macrophages. While previously described functions of NADase pertain to its role upon SLO-mediated translocation into the host cell cytosol, our data suggest that the immune regulatory function of NADase is exerted by nontranslocated enzyme, identifying a previously unrecognized extracellular niche for NADase functionality. This immune regulatory property of extracellular NADase adds another possible explanation to how increased secretion of NADase correlates with bacterial virulence."
5,4,7,7,9,speciation time (small tree),species range,single species in the wild - environment changing,whole genome,Pathogen,Nina Hafer,2017,https://doi.org/10.1128/mSphereDirect.00271-17,"Trivedi, J; Lachapelle, J; Vanderwolf, KJ; Misra, V; Willis, CKR; Ratcliffe, JM; Ness, RW; Anderson, JB; Kohn, LM",Fungus Causing White-Nose Syndrome in Bats Accumulates Genetic Variability in North America with No Sign of Recombination,MSPHERE,2,,,e00271-17,10.1128/mSphereDirect.00271-17,"Emerging fungal diseases of wildlife are on the rise worldwide, and the white-nose syndrome (WNS) epidemic in North American bats is a catastrophic example. The causal agent of WNS is a single clone of the fungus Pseudogymnoascus destructans. Early evolutionary change in this clonal population has major implications for disease ecology and conservation. Accumulation of variation in the fungus through mutation, and shuffling of variation through recombination, could affect the virulence and transmissibility of the fungus and the durability of what appears to be resistance arising in some bat populations. Our genome-wide analysis shows that the clonal population of P. destructans has expanded in size from a single genotype, has begun to accumulate variation through mutation, and presents no evidence as yet of genetic exchange among individuals. IMPORTANCE Since its discovery in 2006, the emerging infectious disease known as white-nose syndrome has killed millions of bats in North America, making it one of the most devastating wildlife epidemics in recorded history. We demonstrate that there has been as yet only spontaneous mutation across the North American population of P. destructans, and we find no indication of recombination. Thus, selective forces, which might otherwise impact pathogenic virulence, have so far had essentially no genetic variation on which to act. Our study confirmed the time of origin for the first and, thus far, only introduction of P. destructans to North America. This system provides an unprecedented opportunity to follow the evolution of a host-pathogen interaction unfolding in real time."
1,1,2,2,2,none,no spatial aspect,single species laboratory system - no environmental aspect,full gene/regulator,Pathogen,Nina Hafer,2017,https://doi.org/10.1371/journal.pntd.0005782,"Ishemgulova, A; Kraeva, N; Hlavacova, J; Zimmer, SL; Butenko, A; Podesvova, L; Lestinova, T; Lukes, J; Kostygov, A; Votypka, J; Volf, P; Yurchenko, V",A putative ATP/GTP binding protein affects Leishmania mexicana growth in insect vectors and vertebrate hosts,PLOS NEGLECTED TROPICAL DISEASES,11,,,e0005782,10.1371/journal.pntd.0005782,"Background Leishmania virulence factors responsible for the complicated epidemiology of the various leishmaniases remain mainly unidentified. This study is a characterization of a gene previously identified as upregulated in two of three overlapping datasets containing putative factors important for Leishmania's ability to establish mammalian intracellular infection and to colonize the gut of an insect vector. Methodology/Principal findings The investigated gene encodes ATP/GTP binding motif-containing protein related to Leishmania development 1 (ALD1), a cytosolic protein that contains a cryptic ATP/GTP binding P-loop. We compared differentiation, growth rates, and infective abilities of wild-type and ALD1 null mutant cell lines of L. mexicana. Loss of ALD1 results in retarded growth kinetics but not defects in differentiation in axenic culture. Similarly, when mice and the sand fly vector were infected with the ALD1 null mutant, the primary difference in infection and colonization phenotype relative to wild type was an inability to achieve maximal host pathogenicity. While ability of the ALD1 null mutant cells to infect macrophages in vitro was not affected, replication within macrophages was clearly curtailed. Conclusions/Significance L. mexicana ALD1, encoding a protein with no assigned functional domains or motifs, was identified utilizing multiple comparative analyses with the related and often experimentally overlooked monoxenous flagellates. We found that it plays a role in Leishmania infection and colonization in vitro and in vivo. Results suggest that ALD1 functions in L. mexicana's general metabolic network, rather than function in specific aspect of virulence as anticipated from the compared datasets. This result validates our comparative genomics approach for finding relevant factors, yet highlights the importance of quality laboratory-based analysis of genes tagged by these methods."
1,3,6,6,4,none,small spatial scale (couple of populations),single species in the wild - environment constant,exome/transcriptome,Host,Nina Hafer,2017,https://doi.org/10.1111/mec.14146,"Bankers, L; Fields, P; McElroy, KE; Boore, JL; Logsdon, JM; Neiman, M",Genomic evidence for population-specific responses to co-evolving parasites in a New Zealand freshwater snail,MOLECULAR ECOLOGY,26,3663,3675,,10.1111/mec.14146,"Reciprocal co-evolving interactions between hosts and parasites are a primary source of strong selection that can promote rapid and often population-or geno-type-specific evolutionary change. These host-parasite interactions are also a major source of disease. Despite their importance, very little is known about the genomic basis of co-evolving host-parasite interactions in natural populations, especially in animals. Here, we use gene expression and sequence evolution approaches to take critical steps towards characterizing the genomic basis of interactions between the freshwater snail Potamopyrgus antipodarum and its co-evolving sterilizing trematode parasite, Microphallus sp., a textbook example of natural coevolution. We found that Microphallus-infected P. antipodarum exhibit systematic downregulation of genes relative to uninfected P. antipodarum. The specific genes involved in parasite response differ markedly across lakes, consistent with a scenario where population-level coevolution is leading to population-specific host-parasite interactions and evolutionary trajectories. We also used an FST-based approach to identify a set of loci that represent promising candidates for targets of parasite-mediated selection across lakes as well as within each lake population. These results constitute the first genomic evidence for population-specific responses to co-evolving infection in the P. antipodarum-Microphallus interaction and provide new insights into the genomic basis of co-evolutionary interactions in nature."
1,1,6,7,2,none,no spatial aspect,single species in the wild - environment constant,whole genome,Host,Nina Hafer,2017,https://doi.org/10.1074/jbc.M117.782425,"Kim, HS; Lee, K; Bae, S; Park, J; Lee, CK; Kim, M; Kim, E; Kim, M; Kim, S; Kim, C; Kim, JS",CRISPR/Cas9-mediated gene knockout screens and target identification via whole-genome sequencing uncover host genes required for picornavirus infection,JOURNAL OF BIOLOGICAL CHEMISTRY,292,10664,10671,,10.1074/jbc.M117.782425,"Several groups have used genome-wide libraries of lentiviruses encoding small guide RNAs (sgRNAs) for genetic screens. In most cases, sgRNA expression cassettes are integrated into cells by using lentiviruses, and target genes are statistically estimated by the readout of sgRNA sequences after targeted sequencing. We present a new virus-free method for human gene knockout screens using a genome-wide library of CRISPR/Cas9 sgRNAs based on plasmids and target gene identification via whole-genome sequencing (WGS) confirmation of authentic mutations rather than statistical estimation through targeted amplicon sequencing. We used 30,840 pairs of individually synthesized oligonucleotides to construct the genome-scale sgRNA library, collectively targeting 10,280 human genes (i.e. three sgRNAs per gene). These plasmid libraries were co-transfected with a Cas9-expression plasmid into human cells, which were then treated with cytotoxic drugs or viruses. Only cells lacking key factors essential for cytotoxic drug metabolism or viral infection were able to survive. Genomic DNA isolated from cells that survived these challenges was subjected to WGS to directly identify CRISPR/Cas9-mediated causal mutations essential for cell survival. With this approach, we were able to identify known and novel genes essential for viral infection in human cells. We propose that genome-wide sgRNA screens based on plasmids coupled with WGS are powerful tools for forward genetics studies and drug target discovery."
6,1,8,1,7,speciation time (large tree),no spatial aspect,multiple species in the wild - environment constant,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Host,Nina Hafer,2017,https://doi.org/10.1186/s12864-017-3839-7,"Goebel, J; Promerova, M; Bonadonna, F; McCoy, KD; Serbielle, C; Strandh, M; Yannic, G; Burri, R; Fumagalli, L",100 million years of multigene family evolution: origin and evolution of the avian MHC class IIB,BMC GENOMICS,18,,,460,10.1186/s12864-017-3839-7,"Background: Gene duplication has led to a most remarkable adaptation involved in vertebrates' host-pathogen arms-race, the major histocompatibility complex (MHC). However, MHC duplication history is as yet poorly understood in non-mammalian vertebrates, including birds. Results: Here, we provide evidence for the evolution of two ancient avian MHC class IIB (MHCIIB) lineages by a duplication event prior to the radiation of all extant birds >100 million years ago, and document the role of concerted evolution in eroding the footprints of the avian MHCIIB duplication history. Conclusions: Our results suggest that eroded footprints of gene duplication histories may mimic birth-death evolution and that in the avian MHC the presence of the two lineages may have been masked by elevated rates of concerted evolution in several taxa. Through the presence of a range of intermediate evolutionary stages along the homogenizing process of concerted evolution, the avian MHCIIB provides a remarkable illustration of the erosion of multigene family duplication history."
1,1,6,6,2,none,no spatial aspect,single species in the wild - environment constant,exome/transcriptome,Pathogen,Nina Hafer,2017,https://doi.org/10.1093/database/bax047,"Torres, F; Arias-Carrasco, R; Caris-Maldonado, JC; Barral, A; Maracaja-Coutinho, V; De Queiroz, ATL",LeishDB: a database of coding gene annotation and non-coding RNAs in Leishmania braziliensis,DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION,NA,,,bax047,10.1093/database/bax047,"Leishmania braziliensis is the etiological agent of cutaneous leishmaniasis, a disease with high public health importance, affecting 12 million people worldwide. Although its genome sequence was originally published in 2007, the two reference public annotations still presents at least 80% of the genes simply classified as hypothetical or putative proteins. Furthermore, it is notable the absence of non-coding RNA (ncRNA) sequences from Leishmania species in public databases. These poorly annotated coding genes and ncRNAs could be important players for the understanding of this protozoan biology, the mechanisms behind host-parasite interactions and disease control. Herein, we performed a new prediction and annotation of L. braziliensis protein-coding genes and non-coding RNAs, using recently developed predictive algorithms and updated databases. In summary, we identified 11 491 ORFs, with 5263 (45.80%) of them associated with proteins available in public databases. Moreover, we identified for the first time the repertoire of 11 243 ncRNAs belonging to different classes distributed along the genome. The accuracy of our predictions was verified by transcriptional evidence using RNA-seq, confirming that they are actually generating real transcripts. These data were organized in a public repository named LeishDB (www.leishdb.com), which represents an improvement on the publicly available data related to genomic annotation for L. braziliensis. This updated information can be useful for future genomics, transcriptomics and metabolomics studies; being an additional tool for genome annotation pipelines and novel studies associated with the understanding of this protozoan genome complexity, organization, biology, and development of innovative methodologies for disease control and diagnostics."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Nina Hafer,2017,https://doi.org/10.1186/s13071-017-2218-1,"Wang, TF; Zhao, M; Liang, D; Bose, U; Kaur, S; McManus, DP; Cummins, SF",Changes in the neuropeptide content of Biomphalaria ganglia nervous system following Schistosoma infection,PARASITES & VECTORS,10,,,275,10.1186/s13071-017-2218-1,"Background: Molluscs, including snails, are prone to parasite infection, which can lead to massive physiological and behavioural changes, yet many of the molecular components involved remain unresolved. Central to this point is the neural system that in snails consists of several ganglia that regulate the animals' physiology and behaviour patterns. The availability of a genomic resource for the freshwater snail Biomphalaria glabrata provides a mean towards the high throughput analysis of changes in the central nervous system (CNS) following infection with Schistosoma miracidia. Results: In this study, we performed a proteomic analysis of the B. glabrata CNS at pre-patent infection, providing a list of proteins that were further used within a protein-protein interaction (PPI) framework against S. mansoni proteins. A hub with most connections for both non-infected and infected Biomphalaria includes leucine aminopeptidase 2 (LAP2), which interacts with numerous miracidia proteins that together belong to the immunoglobulin family of cell adhesion related molecules. We additionally reveal the presence of at least 165 neuropeptides derived from the precursors of buccalin, enterin, FMRF, FVRI, pedal peptide 1, 2, 3 and 4, RYamide, RFamide, pleurin and others. Many of these were present at significantly reduced levels in the snail's CNS post-infection, such as the egg laying hormone, a neuropeptide required to initiate egg laying in gastropod molluscs. Conclusions: Our analysis demonstrates that LAP2 may be a key component that regulates parasite infection physiology, as well as establishing that parasite-induced reproductive castration may be facilitated by significant reductions in reproduction-associated neuropeptides. This work helps in our understanding of molluscan neuropeptides and further stimulates advances in parasite-host interactions."
1,1,6,3,2,none,no spatial aspect,single species in the wild - environment constant,gene family/microsatellites,Host,Nina Hafer,2017,https://doi.org/10.1016/j.gdata.2017.03.014,"Bishnoi, R; Singla, D",APMicroDB: A microsatellite database of Acyrthosiphon pisum,GENOMICS DATA,12,111,115,,10.1016/j.gdata.2017.03.014,"Pea aphids represent a complex genetic system that could be used for QTL analysis, genetic diversity and population genetics studies. Here, we described the development of first microsatellite repeat database of the pea aphid (APMicroDB), accessible at ""http://deepaklab.com/aphidmicrodb"". We identified 3,40,233 SSRs using MI-croSAtellite (MISA) tool that was distributed in 14,067 (out of 23,924) scaffold of the pea aphid. We observed 89.53% simple repeats of which 73.41% were mono-nucleotide, followed by di-nucleotide repeats. This database stored information about the repeats kind, GC content, motif type (mono - hexa), genomic location etc. We have also incorporated the primer information derived from Primer3 software of the 250bp flanking region of the identified marker. Blast tool is also provided for searching the user query sequence for identified marker and their primers. This work has an immense use for scientific community working in the field of agricultural pest management, QTL mapping, and host-pathogen interaction analysis. (C) 2017 The Authors. Published by Elsevier Inc. This"
5,3,6,5,8,speciation time (small tree),small spatial scale (couple of populations),single species in the wild - environment constant,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Pathogen,Nina Hafer,2017,https://doi.org/10.1186/s12864-017-3789-0,"Diallo, K; Gamougam, K; Daugla, DM; Harrison, OB; Bray, JE; Caugant, DA; Lucidarme, J; Trotter, CL; Hassan-King, M; Stuart, JM; Manigart, O; Greenwood, BM; Maiden, MCJ",Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad,BMC GENOMICS,18,,,398,10.1186/s12864-017-3789-0,"Background: Serogroup A Neisseria meningitidis (NmA) was the cause of the 2011 meningitis epidemics in Chad. This bacterium, often carried asymptomatically, is considered to be an ""accidental pathogen""; however, the transition from carriage to disease phenotype remains poorly understood. This study examined the role genetic diversity might play in this transition by comparing genomes from geographically and temporally matched invasive and carried NmA isolates. Results: All 23 NmA isolates belonged to the ST-5 clonal complex (cc5). Ribosomal MLST comparison with other publically available NmA: cc5 showed that isolates were closely related, although those from Chad formed two distinct branches and did not cluster with other NmA, based on their MLST profile, geographical and temporal location. Whole genome MLST (wgMLST) comparison identified 242 variable genes among all Chadian isolates and clustered them into three distinct phylogenetic groups (Clusters 1, 2, and 3): no systematic clustering by disease or carriage source was observed. There was a significant difference (p = 0.0070) between the mean age of the individuals from which isolates from Cluster 1 and Cluster 2 were obtained, irrespective of whether the person was a case or a carrier. Conclusions: Whole genome sequencing provided high-resolution characterization of the genetic diversity of these closely related NmA isolates. The invasive meningococcal isolates obtained during the epidemic were not homogeneous; rather, a variety of closely related but distinct clones were circulating in the human population with some clones preferentially colonizing specific age groups, reflecting a potential age-related niche adaptation. Systematic genetic differences were not identified between carriage and disease isolates consistent with invasive meningococcal disease being a multi-factorial event resulting from changes in host-pathogen interactions along with the bacterium."
5,2,6,7,7,speciation time (small tree),local (one population),single species in the wild - environment constant,whole genome,Pathogen,Nina Hafer,2017,https://doi.org/10.1128/mBio.00489-17,"Long, SW; Olsen, RJ; Eagar, TN; Beres, SB; Zhao, PC; Davis, JJ; Brettin, T; Xia, FF; Musser, JM","Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307",MBIO,8,,,e00489-17,10.1128/mBio.00489-17,"Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae, it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured from patients in the 2,000-bed Houston Methodist Hospital system between September 2011 and May 2015, representing a comprehensive, population-based strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused more infections than those of well-studied epidemic CG258. Strains varied markedly in gene content and had an extensive array of small and very large plasmids, often containing antimicrobial resistance genes. Some patients with multiple strains cultured over time were infected with genetically distinct clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse strains showed that the global transcriptome of each strain was unique and highly variable. Experimental mouse infection provided new information about immunological parameters of host-pathogen interaction. We exploited the large data set to develop whole-genome sequence-based classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research. IMPORTANCE Klebsiella pneumoniae causes human infections that are increasingly difficult to treat because many strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms have caused outbreaks in health care settings worldwide. Using a comprehensive population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused the plurality of ESBL-producing K. pneumoniae infections in our patients. We discovered that CG307 strains have been abundant in Houston for many years. As assessed by experimental mouse infection, CG307 strains were as virulent as pandemic CG258 strains. Our results may portend the emergence of an especially successful clonal group of antibiotic- resistant K. pneumoniae."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Nina Hafer,2017,https://doi.org/10.1016/j.exppara.2017.02.019,"Singh, N; Sundar, S",Integrating genomics and proteomics permits identification of immunodominant antigens associated with drug resistance in human visceral leishmaniasis in India,EXPERIMENTAL PARASITOLOGY,176,30,45,,10.1016/j.exppara.2017.02.019,"Resistance of human pathogens like Leishmania to drugs is a growing concern where the multidrugresistant phenotype renders chemotherapy ineffective. The acquired resistance of Leishmania to antimony has promoted intense research on the mechanisms involved but the question has not been resolved yet. In this study we have explored host-pathogen-drug interactions leading to identification of pharmacological determinants of host macrophages that resist the sodium antimony gluconate (SAG) mediated intracellular parasite killing. mRNA profiling of mammalian host stage amastigotes of sodium antimony gluconate (SAG) 'sensitive' and 'resistant' parasite lines was carried out using Affymetrix GeneChip((R)) Human Genome U133 Plus 2.0 Array. Patient sera was used to identify immunogenic proteins by two-dimensional gel analysis (2DE) and mass spectrometric analysis (LC-MS/MS). Immunofluorescence microscopy confirmed the identities on 'sensitive' and 'resistant' parasite lines. A total of nine immunogenic proteins whose intensities changed significantly and consistently in multiple experiments were detected, suggesting that a cohort of proteins are altered in expression levels in the 'resistant' parasites. Global expression profiling using microarrays revealed this regulation was not reflected by changes in the levels of the cognate mRNAs. Following identification of proteins by mass spectrometry, one such regulated protein, enolase, was chosen for more detailed analysis. Immunofluorescence microscopy employing antisera against this enzyme confirmed that its level was differentially regulated in the 'resistant' isolate. We show that high serum level of immunoreactive protein is associated with 'resistant' phenotype. Differentially expressed proteins with immunomodulatory activities were found to be associated with the 'resistant phenotype'. (C) 2017 Elsevier Inc. All rights reserved."
5,1,9,7,6,speciation time (small tree),no spatial aspect,multiple species in the wild - environment changing,whole genome,Pathogen,Nina Hafer,2017,https://doi.org/10.1186/s12862-017-0935-x,"Flores-Ponce, M; Vallebueno-Estrada, M; Gonzalez-Orozco, E; Ramos-Aboites, HE; Garcia-Chavez, JN; Simoes, N; Montiel, R",Signatures of co-evolutionary host-pathogen interactions in the genome of the entomopathogenic nematode Steinernema carpocapsae,BMC EVOLUTIONARY BIOLOGY,17,,,108,10.1186/s12862-017-0935-x,"Background: The entomopathogenic nematode Steinernema carpocapsae has been used worldwide as a biocontrol agent for insect pests, making it an interesting model for understanding parasite-host interactions. Two models propose that these interactions are co-evolutionary processes in such a way that equilibrium is never reached. In one model, known as ""arms race"", new alleles in relevant genes are fixed in both host and pathogens by directional positive selection, producing recurrent and alternating selective sweeps. In the other model, known as""trench warfare"", persistent dynamic fluctuations in allele frequencies are sustained by balancing selection. There are some examples of genes evolving according to both models, however, it is not clear to what extent these interactions might alter genome-level evolutionary patterns and intraspecific diversity. Here we investigate some of these aspects by studying genomic variation in S. carpocapsae and other pathogenic and free-living nematodes from phylogenetic clades IV and V. Results: To look for signatures of an arms-race dynamic, we conducted massive scans to detect directional positive selection in interspecific data. In free-living nematodes, we detected a significantly higher proportion of genes with sites under positive selection than in parasitic nematodes. However, in these genes, we found more enriched Gene Ontology terms in parasites. To detect possible effects of dynamic polymorphisms interactions we looked for signatures of balancing selection in intraspecific genomic data. The observed distribution of Tajima's D values in S. carpocapsae was more skewed to positive values and significantly different from the observed distribution in the free-living Caenorhabditis briggsae. Also, the proportion of significant positive values of Tajima's D was elevated in genes that were differentially expressed after induction with insect tissues as compared to both non-differentially expressed genes and the global scan. Conclusions: Our study provides a first portrait of the effects that lifestyle might have in shaping the patterns of selection at the genomic level. An arms-race between hosts and pathogens seems to be affecting specific genetic functions but not necessarily increasing the number of positively selected genes. Trench warfare dynamics seem to be acting more generally in the genome, likely focusing on genes responding to the interaction, rather than targeting specific genetic functions."
2,3,6,6,5,within an individuals lifespan (single generation),small spatial scale (couple of populations),single species in the wild - environment constant,exome/transcriptome,Host,Karin Harding,2017,https://doi.org/10.1098/rspb.2017.0029,"Geffre, AC; Liu, RL; Manfredini, F; Beani, L; Kathirithamby, J; Grozinger, CM; Toth, AL",Transcriptomics of an extended phenotype: parasite manipulation of wasp social behaviour shifts expression of caste-related genes,PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES,284,,,20170029,10.1098/rspb.2017.0029,"Parasites can manipulate host behaviour to increase their own transmission and fitness, but the genomic mechanisms by which parasites manipulate hosts are not well understood. We investigated the relationship between the social paper wasp, Polistes dominula, and its parasite, Xenos vesparum (Insecta: Strepsiptera), to understand the effects of an obligate endoparasitoid on its host's brain transcriptome. Previous research suggests that X. vesparum shifts aspects of host social caste-related behaviour and physiology in ways that benefit the parasitoid. We hypothesized that X. vesparum-infested (stylopized) females would showa shift in caste-related brain gene expression. Specifically, we predicted that stylopized females, who would normally be workers, would show gene expression patterns resembling pre-overwintering queens (gynes), reflecting gyne-like changes in behaviour. We used RNA-sequencing data to characterize patterns of brain gene expression in stylopized females and compared these with those of unstylopized workers and gynes. In support of our hypothesis, we found that stylopized females, despite sharing numerous physiological and life-history characteristics with members of the worker caste, show gyne-shifted brain expression patterns. These data suggest that the parasitoid affects its host by exploiting phenotypic plasticity related to social caste, thus shifting naturally occurring social behaviour in a way that is beneficial to the parasitoid."
6,1,1,7,7,speciation time (large tree),no spatial aspect,none - theoretical,whole genome,Pathogen,Karin Harding,2017,https://doi.org/10.1186/s12862-017-0942-y,"Puigbo, P; Makarova, KS; Kristensen, DM; Wolf, YI; Koonin, EV",Reconstruction of the evolution of microbial defense systems,BMC EVOLUTIONARY BIOLOGY,17,,,94,10.1186/s12862-017-0942-y,"Background: Evolution of bacterial and archaeal genomes is a highly dynamic process that involves intensive loss of genes as well as gene gain via horizontal transfer, with a lesser contribution from gene duplication. The rates of these processes can be estimated by comparing genomes that are linked by an evolutionary tree. These estimated rates of genome dynamics events substantially differ for different functional classes of genes. The genes involved in defense against viruses and other invading DNA are among those that are gained and lost at the highest rates. Results: We employed a stochastic birth- and- death model to obtain maximum likelihood estimates of the rates of gain and loss of defense genes in 35 groups of closely related bacterial genomes and one group of archaeal genomes. We find that on average, the defense genes experience 1.4 fold higher flux than the rest of microbial genes. This excessive flux of defense genes over the genomic mean is consistent across diverse microbial groups. The few exceptions include intracellular parasites with small, degraded genomes that possess few defense systems which are more stable than in other microbes. Generally, defense genes follow the previously established pattern of genome dynamics, with gene family loss being about 3 times more common than gain and an order of magnitude more common than expansion or contraction of gene families. Case by case analysis of the evolutionary dynamics of defense genes indicates frequent multiple events in the same locus and widespread involvement of mobile elements in the gain and loss of defense genes. Conclusions: Evolution of microbial defense systems is highly dynamic but, notwithstanding the host- parasite arms race, generally follows the same trends that have been established for the rest of the genes. Apart from the paucity and the low flux of defense genes in parasitic bacteria with deteriorating genomes, there is no clear connection between the evolutionary regime of defense systems and microbial life style."
2,1,2,3,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,gene family/microsatellites,Host,Karin Harding,2017,https://doi.org/10.1038/srep45620,"Niu, J; Meeus, I; De Coninck, DI; Deforce, D; Etebari, K; Asgari, S; Smagghe, G","Infections of virulent and avirulent viruses differentially influenced the expression of dicer-1, ago-1, and microRNAs in Bombus terrestris",SCIENTIFIC REPORTS,7,,,45620,10.1038/srep45620,"The microRNA (miRNA) pathway is well established to be involved in host-pathogen interactions. As key insect pollinators, bees are suffering from widely spreading viruses, especially honeybees and bumblebees. In order to better understand bee-virus interaction, we comparatively analyzed the involvement of the bumblebee miRNA pathway upon infection by two different viruses. In our setup, an avirulent infection is induced by slow bee paralysis virus (SBPV) and a virulent infection is induced by Israeli acute paralysis virus (IAPV). Our results showed the increased expressions of dicer-1 and ago-1 upon SBPV infection. There were 17 and 12 bumblebee miRNAs differentially expressed upon SBPV and IAPV infections, respectively. These results may indicate the involvement of the host miRNA pathway in bumblebee-virus interaction. However, silencing of dicer-1 did not influence the genome copy number of SBPV. Target prediction for these differentially expressed miRNAs showed their possible involvement in targeting viral genomic RNA and in the regulation of networks in bumblebee. Our study opens a new insight into bee-virus interaction meditated by host miRNAs."
3,1,5,7,4,few generations,no spatial aspect,multiple species laboratory system - environmental aspect present,whole genome,both,Karin Harding,2017,https://doi.org/10.1111/mec.13906,"Ford, SA; Williams, D; Paterson, S; King, KC",Co-evolutionary dynamics between a defensive microbe and a pathogen driven by fluctuating selection,MOLECULAR ECOLOGY,26,1778,1789,,10.1111/mec.13906,"Microbes that protect their hosts from pathogenic infection are widespread components of the microbiota of both plants and animals. It has been found that interactions between defensive' microbes and pathogens can be genotype-specific and even underlie the variation in host resistance to pathogenic infection. These observations suggest a dynamic co-evolutionary association between pathogens and defensive microbes, but direct evidence of co-evolution is lacking. We tested the hypothesis that defensive microbes and pathogens could co-evolve within host populations by co-passaging a microbe with host-defensive properties (Enterococcus faecalis) and a pathogen (Staphylococcus aureus) within Caenorhabditis elegans nematodes. Using both phenotypic and genomic analyses across evolutionary time, we found patterns of pathogen local adaptation and defensive microbe-pathogen co-evolution via fluctuating selection dynamics. Moreover, co-evolution with defensive microbes resulted in more rapid and divergent pathogen evolution compared to pathogens evolved independently in host populations. Taken together, our results indicate the potential for defensive microbes and pathogens to co-evolve, driving interaction specificity and pathogen evolutionary divergence in the absence of host evolution."
1,3,7,7,4,none,small spatial scale (couple of populations),single species in the wild - environment changing,whole genome,Host,Karin Harding,2017,https://doi.org/10.1111/evo.13209,"Bourgeois, Y; Roulin, AC; Muller, K; Ebert, D",Parasitism drives host genome evolution: Insights from the Pasteuria ramosa-Daphnia magna system,EVOLUTION,71,1106,1113,,10.1111/evo.13209,"Because parasitism is thought to play a major role in shaping host genomes, it has been predicted that genomic regions associated with resistance to parasites should stand out in genome scans, revealing signals of selection above the genomic background. To test whether parasitism is indeed such a major factor in host evolution and to better understand host-parasite interaction at the molecular level, we studied genome-wide polymorphisms in 97 genotypes of the planktonic crustacean Daphnia magna originating from three localities across Europe. Daphniamagna is known to coevolve with the bacterial pathogen Pasteuria ramosa for which host genotypes (clonal lines) are either resistant or susceptible. Using association mapping, we identified two genomic regions involved in resistance to P. ramosa, one of which was already known from a previous QTL analysis. We then performed a naive genome scan to test for signatures of positive selection and found that the two regions identified with the association mapping further stood out as outliers. Several other regions with evidence for selection were also found, but no link between these regions and phenotypic variation could be established. Our results are consistent with the hypothesis that parasitism is driving host genome evolution."
2,3,7,1,5,within an individuals lifespan (single generation),small spatial scale (couple of populations),single species in the wild - environment changing,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Karin Harding,2017,https://doi.org/10.1016/j.parint.2016.12.008,"Huyse, T; Oeyen, M; Larmuseau, MHD; Volckaert, FAM",Co-phylogeographic study of the flatworm Gyrodactylus gondae and its goby host Pomatoschistus minutus,PARASITOLOGY INTERNATIONAL,66,119,125,,10.1016/j.parint.2016.12.008,"We performed a comparative phylogeographic study on the monogenean flatworm Gyrodactylus gondae Huyse, Malmberg & Volckaert 2005 (Gyrodactylidae) and its sand goby host Pomatoschistus minutus (Pallas, 1770) (Gobiidae). G. gondae is a host-specific parasite with a direct life cycle and a very short generation time. These properties are expected to increase the chance to track the genealogical history of the host with genetic data of the parasite ('magnifying glass principle'). To investigate this hypothesis we screened nine sand goby populations (n = 326) along the Atlantic coasts of Europe for Gyrodactylus specimens. Low parasite prevalence resulted in partially overlapping host and parasite datasets. Ninety-two G. gondae collected on five sand goby populations were subsequently sequenced for a 460 bp cytochrome c oxidase subunit II (coxII) fragment, which, in combination with previously published haplotype data for the hosts, allowed for partially overlapping host and parasite datasets. Haplotype diversity was lowest in the Irish Sea while nucleotide diversity was highest in the Southern North Sea. The host population also showed the lowest diversity in the Irish Sea but the highest nucleotide diversity, based on cytochrome b sequences of 850 bp, was found in Skagerrak. Phylogeographic networks suggest postglacial expansion in both the host and the parasite. Pair-wise population differentiation was however not consistently higher in the parasite than in the host, rejecting the magnifying glass hypothesis for this host-parasite system. The parasite network offered limited resolution and was characterized by many extinctions and/or missing haplotypes, which could be attributed to 1) sampling bias, 2) size fluctuations in the parasite populations resulting in frequent extinctions and genetic drift and 3) the relatively young age of the host-parasite association. A more exhaustive study including a broader geographical and genomic coverage is needed to discriminate among these competing hypotheses. (C) 2016 Published by Elsevier Ireland Ltd."
5,3,7,7,8,speciation time (small tree),small spatial scale (couple of populations),single species in the wild - environment changing,whole genome,Pathogen,Karin Harding,2017,https://doi.org/10.3389/fcimb.2017.00088,"Jia, XM; Yang, L; Dong, MX; Chen, ST; Lv, LN; Cao, DD; Fu, J; Yang, TT; Zhang, J; Zhang, XL; Shang, YY; Wang, GR; Sheng, YJ; Huang, HR; Chen, F","The Bioinformatics Analysis of Comparative Genomics of Mycobacterium tuberculosis Complex (MTBC) Provides Insight into Dissimilarities between Intraspecific Groups Differingin Host Association, Virulence, and Epitope Diversity",FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,7,,,88,10.3389/fcimb.2017.00088,"Tuberculosis now exceeds HIV as the top infectious disease cause of mortality, and is caused by the Mycobacterium tuberculosis complex (MTBC). MTBC strains have highly conserved genome sequences (similarity >99%) but dramatically different phenotypes. To analyze the relationship between genotype and phenotype, we conducted the comparative genomic analysis on 12 MTBC strains representing different lineages (i.e., Mycobacterium bovis; M. bovis BCG; M. microti; M. africanum; M. tuberculosis H37Rv; M. tuberculosis H37Ra, and six M. tuberculosis clinical isolates). The analysis focused on the three aspects of pathogenicity: host association, virulence, and epitope variations. Host association analysis indicated that eight mce3 genes, two enoyl-CoA hydratases, and five PE/PPE family genes were present only in human isolates; these may have roles in host-pathogen interactions. There were 15 SNPs found on virulence factors (including five SNPs in three ESX secretion proteins) only in the Beijing strains, which might be related to their more virulent phenotype. A comparison between the virulent H37Rv and non-virulent H37Ra strains revealed three SNPs that were likely associated with the virulence attenuation of H37Ra: S219L (PhoP), A219E (MazG) and a newly identified I228M (EspK). Additionally, a comparison of animal-associated MTBC strains showed that the deletion of the first four genes (i.e., pe35, ppe68, esxB, esxA), rather than all eight genes of RD1, might play a central role in the virulence attenuation of animal isolates. Finally, by comparing epitopes among MTBC strains, we found that four epitopes were lost only in the Beijing strains; this may render them better capable of evading the human immune system, leading to enhanced virulence. Overall, our comparative genomic analysis of MTBC strains reveals the relationship between the highly conserved genotypes and the diverse phenotypes of MTBC, provides insight into pathogenic mechanisms, and facilitates the development of potential molecular targets for the prevention and treatment of tuberculosis."
5,1,4,7,6,speciation time (small tree),no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Pathogen,Karin Harding,2017,https://doi.org/10.1038/ncomms14742,"Farrer, RA; Martel, A; Verbrugghe, E; Abouelleil, A; Ducatelle, R; Longcore, JE; James, TY; Pasmans, F; Fisher, MC; Cuomo, CA",Genomic innovations linked to infection strategies across emerging pathogenic chytrid fungi,NATURE COMMUNICATIONS,8,,,14742,10.1038/ncomms14742,"To understand the evolutionary pathways that lead to emerging infections of vertebrates, here we explore the genomic innovations that allow free-living chytrid fungi to adapt to and colonize amphibian hosts. Sequencing and comparing the genomes of two pathogenic species of Batrachochytrium to those of close saprophytic relatives reveals that pathogenicity is associated with remarkable expansions of protease and cell wall gene families, while divergent infection strategies are linked to radiations of lineage-specific gene families. By comparing the host-pathogen response to infection for both pathogens, we illuminate the traits that underpin a strikingly different immune response within a shared host species. Our results show that, despite commonalities that promote infection, specific gene-family radiations contribute to distinct infection strategies. The breadth and evolutionary novelty of candidate virulence factors that we discover underscores the urgent need to halt the advance of pathogenic chytrids and prevent incipient loss of biodiversity."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Karin Harding,2017,https://doi.org/10.3389/fpls.2017.00370,"Puigvert, M; Guarischi-Sousa, R; Zuluaga, P; Coll, NS; Macho, AP; Setubal, JC; Valls, M",Transcriptomes of Ralstonia solanacearum during Root Colonization of Solanum commersonii,FRONTIERS IN PLANT SCIENCE,8,,,370,10.3389/fpls.2017.00370,"Bacterial wilt of potatoes-also called brown rot-is a devastating disease caused by the vascular pathogen Ralstonia solanacearum that leads to significant yield loss. As in other plant-pathogen interactions, the first contacts established between the bacterium and the plant largely condition the disease outcome. Here, we studied the transcriptome of R. solanacearum UY031 early after infection in two accessions of the wild potato Solanum commersonii showing contrasting resistance to bacterial wilt. Total RNAs obtained from asymptomatic infected roots were deep sequenced and for 4,609 out of the 4,778 annotated genes in strain UY031 were recovered. Only 2 genes were differentially-expressed between the resistant and the susceptible plant accessions, suggesting that the bacterial component plays a minor role in the establishment of disease. On the contrary, 422 genes were differentially expressed (DE) in planta compared to growth on a synthetic rich medium. Only 73 of these genes had been previously identified as DE in a transcriptome of R. solanacearum extracted from infected tomato xylem vessels. Virulence determinants such as the Type Three Secretion System (T3SS) and its effector proteins, motility structures, and reactive oxygen species (ROS) detoxifying enzymes were induced during infection of S. commersonii. On the contrary, metabolic activities were mostly repressed during early root colonization, with the notable exception of nitrogen metabolism, sulfate reduction and phosphate uptake. Several of the R. solanacearum genes identified as significantly up-regulated during infection had not been previously described as virulence factors. This is the first report describing the R. solanacearum transcriptome directly obtained from infected tissue and also the first to analyze bacterial gene expression in the roots, where plant infection takes place. We also demonstrate that the bacterial transcriptome in planta can be studied when pathogen numbers are low by sequencing transcripts from infected tissue avoiding prokaryotic RNA enrichment."
5,5,3,7,10,speciation time (small tree),global spatial scale,single species laboratory system - environmental aspect present,whole genome,Pathogen,Karin Harding,2017,https://doi.org/10.1128/mSystems.00186-16,"Becavin, C; Koutero, M; Tchitchek, N; Cerutti, F; Lechat, P; Maillet, N; Hoede, C; Chiapello, H; Gaspin, C; Cossart, P",Listeriomics: an Interactive Web Platform for Systems Biology of Listeria,MSYSTEMS,2,,,UNSP e00186-16,10.1128/mSystems.00186-16,"As for many model organisms, the amount of Listeria omics data produced has recently increased exponentially. There are now >80 published complete Listeria genomes, around 350 different transcriptomic data sets, and 25 proteomic data sets available. The analysis of these data sets through a systems biology approach and the generation of tools for biologists to browse these various data are a challenge for bioinformaticians. We have developed a web-based platform, named Listeriomics, that integrates different tools for omics data analyses, i.e., (i) an interactive genome viewer to display gene expression arrays, tiling arrays, and sequencing data sets along with proteomics and genomics data sets; (ii) an expression and protein atlas that connects every gene, small RNA, antisense RNA, or protein with the most relevant omics data; (iii) a specific tool for exploring protein conservation through the Listeria phylogenomic tree; and (iv) a coexpression network tool for the discovery of potential new regulations. Our platform integrates all the complete Listeria species genomes, transcriptomes, and proteomes published to date. This website allows navigation among all these data sets with enriched metadata in a user-friendly format and can be used as a central database for systems biology analysis. IMPORTANCE In the last decades, Listeria has become a key model organism for the study of host-pathogen interactions, noncoding RNA regulation, and bacterial adaptation to stress. To study these mechanisms, several genomics, transcriptomics, and proteomics data sets have been produced. We have developed Listeriomics, an interactive web platform to browse and correlate these heterogeneous sources of information. Our website will allow listeriologists and microbiologists to decipher key regulation mechanism by using a systems biology approach."
5,3,3,7,8,speciation time (small tree),small spatial scale (couple of populations),single species laboratory system - environmental aspect present,whole genome,Pathogen,Karin Harding,2017,https://doi.org/10.1371/journal.ppat.1006252,"Kerr, PJ; Cattadori, IM; Rogers, MB; Fitch, A; Geber, A; Liu, J; Sim, DG; Boag, B; Eden, JS; Ghedin, E; Read, AF; Holmes, EC",Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia,PLOS PATHOGENS,13,,,e1006252,10.1371/journal.ppat.1006252,"The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954 - 1955) and between 2008 - 2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms."
1,3,6,6,4,none,small spatial scale (couple of populations),single species in the wild - environment constant,exome/transcriptome,Pathogen,Karin Harding,2017,https://doi.org/10.1534/g3.116.037275,"Bankers, L; Neiman, M",De Novo Transcriptome Characterization of a Sterilizing Trematode Parasite (Microphallus sp.) from Two Species of New Zealand Snails,G3-GENES GENOMES GENETICS,7,871,880,,10.1534/g3.116.037275,"Snail-borne trematodes represent a large, diverse, and evolutionarily, ecologically, and medically important group of parasites, often imposing strong selection on their hosts and causing host morbidity and mortality. Even so, there are very few genomic and transcriptomic resources available for this important animal group. We help to fill this gap by providing transcriptome resources from trematode metacercariae infecting two congeneric snail species, Potamopyrgus antipodarum and P. estuarinus. This genus of New Zealand snails has gained prominence in large part through the development of P. antipodarum and its sterilizing trematode parasite Microphallus livelyi into a textbook model for host-parasite coevolutionary interactions in nature. By contrast, the interactions between Microphallus trematodes and P. estuarinus, an estuary-inhabiting species closely related to the freshwater P. antipodarum, are relatively unstudied. Here, we provide the first annotated transcriptome assemblies from Microphallus isolated from P. antipodarum and P. estuarinus. We also use these transcriptomes to produce genomic resources that will be broadly useful to those interested in host-parasite coevolution, local adaption, and molecular evolution and phylogenetics of this and other snail-trematode systems. Analyses of the two Microphallus transcriptomes revealed that the two trematode types are more genetically differentiated from one another than are the M. livelyi infecting different populations of P. antipodarum, suggesting that the Microphallus infecting P. estuarinus represent a distinct lineage. We also provide a promising set of candidate genes likely involved in parasitic infection and response to salinity stress."
1,2,6,7,3,none,local (one population),single species in the wild - environment constant,whole genome,Pathogen,Karin Harding,2017,https://doi.org/10.1007/s00251-016-0960-8,"Antonides, J; Ricklefs, R; DeWoody, JA",The genome sequence and insights into the immunogenetics of the bananaquit (Passeriformes: Coereba flaveola),IMMUNOGENETICS,69,175,186,,10.1007/s00251-016-0960-8,"Avian genomics, especially of non-model species, is in its infancy relative to mammalian genomics. Here, we describe the sequencing, assembly, and annotation of a new avian genome, that of the bananaquit Coereba flaveola (Passeriformes: Thraupidae). We produced similar to 30-fold coverage of the genome with an assembly size of ca. 1.2 Gb, including approximately 16,500 annotated genes. Passerine birds, such as the bananaquit, are commonly infected by avian malarial parasites (Haemosporida), which presumably drive adaptive evolution of immunogenetic loci within the host genome. In the context of our research on the distribution of avian Haemosporida, we specifically characterized immune loci, including toll-like receptor (TLR) and major histocompatibility complex (MHC) genes. Additionally, we identified novel molecular markers in the form of single nucleotide polymorphisms (SNPs), both genome-wide and within identified immune loci. We discovered nine TLR genes and four MHC genes and identified five other TLR- or MHC- associated genes. Genome-wide, over 6 million high-quality SNPs were annotated, including 568 within TLR genes and 102 in MHC genes. This newly described genome and immune characterization expands the knowledge base for avian genomics and phylogenetics and allows for immune genotyping in the bananaquit, providing tools for the investigation of host-parasite coevolution."
1,3,6,6,4,none,small spatial scale (couple of populations),single species in the wild - environment constant,exome/transcriptome,Pathogen,Karin Harding,2017,https://doi.org/10.1094/PHYTO-05-16-0197-R,"Busse, F; Bartkiewicz, A; Terefe-Ayana, D; Niepold, F; Schleusner, Y; Flath, K; Sommerfeldt-Impe, N; Lubeck, J; Strahwald, J; Tacke, E; Hofferbert, HR; Linde, M; Przetakiewicz, J; Debener, T","Genomic and Transcriptomic Resources for Marker Development in Synchytrium endobioticum, an Elusive but Severe Potato Pathogen",PHYTOPATHOLOGY,107,322,328,,10.1094/PHYTO-05-16-0197-R,"Synchytrium endobioticum is an obligate biotrophic fungus that causes wart diseases in potato. Like other species of the class Chytridiomycetes, it does not form mycelia and its zoospores are small, approximately 3 pin in diameter, which complicates the detection of early stages of infection. Furthermore, potato wart disease is difficult to control because belowground organs are infected and resting spores of the fungus are extremely durable. Thus, S. endobioticum is classified as a quarantine organism. More than 40 S. endobioticum pathotypes have been reported, of which pathotypes 1(D1), 2(G1), 6(O1), 8(F1), and 18(T1) are the most important in Germany. No molecular methods for the differentiation of pathotypes are available to date. In this work, we sequenced both genomic DNA and cDNA of the German pathotype 18(T1) from infected potato tissue and generated 5,422 expressed sequence tags (EST) and 423 genomic contigs. Comparative sequencing of 33 genes, single-stranded confirmation polymorphism (SSCP) analysis with polymerase chain reaction fragments of 27 additional genes, as well as the analysis of 41 simple sequence repeat (SSR) loci revealed extremely low levels of variation among five German pathotypes. From these markers, one sequence-characterized amplified region marker and five SSR markers revealed polymorphisms among the German pathotypes and an extended set of 11 additional European isolates. Pathotypes 8(F1) and 18(T1) displayed discrete polymorphisms which allow their differentiation from other pathotypes. Overall, using the information of the six markers, the 16 isolates could be differentiated into three distinct genotype groups. In addition to the presented markers, the new collection of EST from genus Synchytrium might serve in the future for molecular taxonomic studies as well as for analyses of the host pathogen interactions in this difficult pathosystem."
1,3,7,7,4,none,small spatial scale (couple of populations),single species in the wild - environment changing,whole genome,Pathogen,Elin Videvall,2017,https://doi.org/10.1186/s12864-017-3524-x,"Laurent, B; Moinard, M; Spataro, C; Ponts, N; Barreau, C; Foulongne-Oriol, M",Landscape of genomic diversity and host adaptation in Fusarium graminearum,BMC GENOMICS,18,,,203,10.1186/s12864-017-3524-x,"Background: Fusarium graminearum is one of the main causal agents of the Fusarium Head Blight, a worldwide disease affecting cereal cultures, whose presence can lead to contaminated grains with chemically stable and harmful mycotoxins. Resistant cultivars and fungicides are frequently used to control this pathogen, and several observations suggest an adaptation of F. graminearum that raises concerns regarding the future of current plant disease management strategies. To understand the genetic basis as well as the extent of its adaptive potential, we investigated the landscape of genomic diversity among six French isolates of F. graminearum, at single-nucleotide resolution using whole-genome re-sequencing. Results: A total of 242,756 high-confidence genetic variants were detected when compared to the reference genome, among which 96% are single nucleotides polymorphisms. One third of these variants were observed in all isolates. Seventy-seven percent of the total polymorphism is located in 32% of the total length of the genome, comprising telomeric/subtelomeric regions as well as discrete interstitial sections, delineating clear variant enriched genomic regions-7.5 times in average. About 80% of all the F. graminearum protein-coding genes were found polymorphic. Biological functions are not equally affected: genes potentially involved in host adaptation are preferentially located within polymorphic islands and show greater diversification rate than genes fulfilling basal functions. We further identified 29 putative effector genes enriched with non-synonymous effect mutation. Conclusions: Our results highlight a remarkable level of polymorphism in the genome of F. graminearum distributed in a specific pattern. Indeed, the landscape of genomic diversity follows a bi-partite organization of the genome according to polymorphism and biological functions. We measured, for the first time, the level of sequence diversity for the entire gene repertoire of F. graminearum and revealed that the majority are polymorphic. Those assumed to play a role in host-pathogen interaction are discussed, in the light of the subsequent consequences for host adaptation. The annotated genetic variants discovered for this major pathogen are valuable resources for further genetic and genomic studies."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Elin Videvall,2017,https://doi.org/10.1093/gigascience/gix008,"Dong, XF; Armstrong, SD; Xia, D; Makepeace, BL; Darby, AC; Kadowaki, T","Draft genome of the honey bee ectoparasitic mite, Tropilaelaps mercedesae, is shaped by the parasitic life history",GIGASCIENCE,6,,,,10.1093/gigascience/gix008,"The number of managed honey bee colonies has considerably decreased in many developed countries in recent years and ectoparasitic mites are considered as major threats to honey bee colonies and health. However, their general biology remains poorly understood. We sequenced the genome of Tropilaelaps mercedesae, the prevalent ectoparasitic mite infesting honey bees in Asia, and predicted 15 190 protein-coding genes that were well supported by the mite transcriptomes and proteomic data. Although amino acid substitutions have been accelerated within the conserved core genes of two mites, T. mercedesae and Metaseiulus occidentalis, T. mercedesae has undergone the least gene family expansion and contraction between the seven arthropods we tested. The number of sensory system genes has been dramatically reduced, but T. mercedesae contains all gene sets required to detoxify xenobiotics. T. mercedesae is closely associated with a symbiotic bacterium (Rickettsiella grylli-like) and Deformed Wing Virus, the most prevalent honey bee virus. T. mercedesae has a very specialized life history and habitat as the ectoparasitic mite strictly depends on the honey bee inside a stable colony. Thus, comparison of the genome and transcriptome sequences with those of a tick and free-living mites has revealed the specific features of the genome shaped by interaction with the honey bee and colony environment. Genome and transcriptome sequences of T. mercedesae, as well as Varroa destructor (another globally prevalent ectoparasitic mite of honey bee), not only provide insights into the mite biology, but may also help to develop measures to control the most serious pests of the honey bee."
2,1,2,5,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Pathogen,Elin Videvall,2017,https://doi.org/10.1186/s12985-017-0699-3,"Xu, DL; Zhou, GH",Characteristics of siRNAs derived from Southern rice black-streaked dwarf virus in infected rice and their potential role in host gene regulation,VIROLOGY JOURNAL,14,,,27,10.1186/s12985-017-0699-3,"Background: Virus-derived siRNAs (vsiRNAs)-mediated RNA silencing plays important roles in interaction between plant viruses and their hosts. Southern rice black-streaked dwarf virus (SRBSDV) is a newly emerged devastating rice reovirus with ten dsRNA genomic segments. The characteristics of SRBSDV-derived siRNAs and their biological implications in SRBSDV-rice interaction remain unexplored. Methods: VsiRNAs profiling from SRBSDV-infected rice samples was done via small RNA deep sequencing. The putative rice targets of abundantly expressed vsiRNAs were bioinformatically predicted and subjected to functional annotation. Differential expression analysis of rice targets and RNA silencing components between infected and healthy samples was done using RT-qPCR. Results: The vsiRNA was barely detectable at 14 days post infection (dpi) but abundantly present along with elevated expression level of the viral genome at 28 dpi. From the 28-dpi sample, 70,878 reads of 18 similar to 30-nt vsiRNAs were recognized (which mostly were 21-nt and 22-nt), covering 75 similar to 91% of the length of the ten genomic segments respectively. 86% of the vsiRNAs had a < 50% GC content and 79% of them were 5'-uridylated or adenylated. The production of vsiRNAs had no strand polarity but varied among segment origins. Each segment had a few hotspot regions where vsiRNAs of high abundance were produced. 151 most abundant vsiRNAs were predicted to target 844 rice genes, including several types of host resistance or pathogenesis related genes encoding F-box/LRR proteins, receptor-like protein kinases, universal stress proteins, tobamovirus multiplication proteins, and RNA silencing components OsDCL2a and OsAGO17 respectively, some of which showed down regulation in infected plants in RT-qPCR. GO and KEGG classification showed that a majority of the predicted targets were related to cell parts and cellular processes and involved in carbohydrate metabolism, translation, and signal transduction. The silencing component genes OsDCL2a, OsDCL2b, OsDCL4, and OsAGO18 were down regulated, while OsAGO1d, OsAGO2, OsRDR1 and OsRDR6 were up regulated, significantly, upon SRBSDV infection. Conclusions: SRBSDV can regulate the expression of rice RNA silencing pathway components and the virus might compromise host defense and influence host pathogenesis via siRNA pathways."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,both,Elin Videvall,2017,https://doi.org/10.1016/j.fsi.2017.01.005,"Dettleff, P; Moen, T; Santi, N; Martinez, V",Transcriptomic analysis of spleen infected with infectious salmon anemia virus reveals distinct pattern of viral replication on resistant and susceptible Atlantic salmon (Salmo salar),FISH & SHELLFISH IMMUNOLOGY,61,187,193,,10.1016/j.fsi.2017.01.005,"The infectious salmon anemia virus (ISAv) produces a systemic infection in salmonids, causing large losses in salmon production. However, little is known regarding the mechanisms exerting disease resistance. In this paper, we perform an RNA-seq analysis in Atlantic salmon challenged with ISAv (using individuals coming from families that were highly susceptible or highly resistant to ISAv infection). We evaluated the differential expression of both host and ISAv genes in a target organ for the virus, i.e. the spleen. The results showed differential expression of host genes related to response to stress, immune response and protein folding (genes such as; atf3, mhc, mx1-3, cd276, cd2; cocsl, c7, il10, illOrb, ill3ra2, ubl-1, (ng, ifngr1, hivep2, siglel4 and sigle5). An increased protein processing activity was found in susceptible fish, which generates a subsequent unfolded protein response. We observed extreme differences in the expression of viral segments between susceptible and resistant groups, demonstrating the capacity of resistant fish to overcome the virus replication, generating a very low viral load. This phenomenon and survival of this higher resistant fish seem to be related to differences in immune and translational process, as well as to the increase of HIV-EP2 (hivep2) transcript in resistant fish, although the causal mechanism is yet to be discovered. This study provides valuable information about disease resistance mechanisms in Atlantic salmon from a host -pathogen interaction point of view. (C) 2017 Elsevier Ltd. All rights reserved."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Elin Videvall,2017,https://doi.org/10.1016/j.procbio.2016.12.001,"Yun, EJ; Lee, SH; Kim, S; Kim, SH; Kim, KH",Global profiling of metabolic response of Caenorhabditis elegans against Escherichia coli O157:H7,PROCESS BIOCHEMISTRY,53,36,43,,10.1016/j.procbio.2016.12.001,"The pathogenicity of enterohemorrhagic Escherichia coli O157:H7 were extensively studied by genomic and proteomic approaches. However, the possible virulence mechanism of E. coli O157:H7 in its hosts has never been studied using a metabolomic approach. In this study, the intracellular metabolites of C. elegans fed with pathogenic E. coli O157:H7 and non-pathogenic E. colt were profiled by gas chromatography/time-of-flight mass spectrometry. In C. elegans fed with O157:H7, the levels of metabolites related to the mammalian target of rapamycin (mTOR) signaling pathway, such as amino acids and glucose, highly increased. In addition, the levels of metabolites related to lipid oxidation and nucleotide salvage pathways increased. The metabolic intermediates of organic acidurias and atypical hemolytic uremic syndrome also increased when fed with O157:H7. However, the level of trehalose, an mTOR-independent autophagy enhancer, decreased in C. elegans fed with O157:H7. These results showed that infection with O157:H7 alters intracellular metabolite abundance in C. elegans. This study suggest that the metabolomics may be applied to elucidating the virulence mechanisms of pathogenic bacteria. (C) 2016 Elsevier Ltd. All rights reserved."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,both,Elin Videvall,2017,https://doi.org/10.3389/fcimb.2016.00204,"Noroy, C; Meyer, DF",Comparative Genomics of the Zoonotic Pathogen Ehrlichia chaffeensis Reveals Candidate Type IV Effectors and Putative Host Cell Targets,FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,6,,,204,10.3389/fcimb.2016.00204,"During infection, some intracellular pathogenic bacteria use a dedicated multiprotein complex known as the type IV secretion system to deliver type IV effector (T4E) proteins inside the host cell. These T4Es allow the bacteria to evade host defenses and to subvert host cell processes to their own advantage. Ehrlichia chaffeensis is a tick-transmitted obligate intracellular pathogenic bacterium, which causes human monocytic ehrlichiosis. Using comparative whole genome analysis, we identified the relationship between eight available E. chaffeensis genomes isolated from humans and show that these genomes are highly conserved. We identified the candidate core type IV effectome of E. chaffeensis and some conserved intracellular adaptive strategies. We assigned the West Paces strain to genetic group II and predicted the repertoires of T4Es encoded by E. chaffeensis genomes, as well as some putative host cell targets. We demonstrated that predicted T4Es are preferentially distributed in gene sparse regions of the genome. In addition to the identification of the two known type IV effectors of Anaplasmataceae, we identified two novel candidates T4Es, ECHLIB_RS02720 and ECHLIB_RS04640, which are not present in all E. chaffeensis strains and could explain some variations in inter-strain virulence. We also identified another novel candidate T4E, ECHLIB_RS02720, a hypothetical protein exhibiting EPIYA, and NLS domains as well as a classical type IV secretion signal, suggesting an important role inside the host cell. Overall, our results agree with current knowledge of Ehrlichia molecular pathogenesis, and reveal novel candidate T4Es that require experimental validation. This work demonstrates that comparative effectomics enables identification of important host pathways targeted by the bacterial pathogen. Our study, which focuses on the type IV effector repertoires among several strains of E. chaffeensis species, is an original approach and provides rational putative targets for the design of alternative therapeutics against intracellular pathogens. The collection of putative effectors of E. chaffeensis described in our paper could serve as a roadmap for future studies of the function and evolution of effectors."
5,1,4,7,6,speciation time (small tree),no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Pathogen,Elin Videvall,2017,https://doi.org/10.1186/s12862-017-0881-7,"Willemsen, A; Zwart, MP; Elena, SF",High virulence does not necessarily impede viral adaptation to a new host: a case study using a plant RNA virus,BMC EVOLUTIONARY BIOLOGY,17,,,25,10.1186/s12862-017-0881-7,"Background: Theory suggests that high virulence could hinder between-host transmission of microparasites, and that virulence therefore will evolve to lower levels. Alternatively, highly virulent microparasites could also curtail host development, thereby limiting both the host resources available to them and their own within-host effective population size. In this case, high virulence might restrain the mutation supply rate and increase the strength with which genetic drift acts on microparasite populations. Thereby, this alternative explanation limits the microparasites' potential to adapt to the host and ultimately the ability to evolve lower virulence. As a first exploration of this hypothesis, we evolved Tobacco etch virus carrying an eGFP fluorescent marker in two semi-permissive host species, Nicotiana benthamiana and Datura stramonium, for which it has a large difference in virulence. We compared the results to those previously obtained in the natural host, Nicotiana tabacum, where we have shown that carriage of eGFP has a high fitness cost and its loss serves as a real-time indicator of adaptation. Results: After over half a year of evolution, we sequenced the genomes of the evolved lineages and measured their fitness. During the evolution experiment, marker loss leading to viable virus variants was only observed in one lineage of the host for which the virus has low virulence, D. stramonium. This result was consistent with the observation that there was a fitness cost of eGFP in this host, while surprisingly no fitness cost was observed in the host for which the virus has high virulence, N. benthamiana. Furthermore, in both hosts we observed increases in viral fitness in few lineages, and host-specific convergent evolution at the genomic level was only found in N. benthamiana. Conclusions: The results of this study do not lend support to the hypothesis that high virulence impedes microparasites' evolution. Rather, they exemplify that jumps between host species can be game changers for evolutionary dynamics. When considering the evolution of genome architecture, host species jumps might play a very important role, by allowing evolutionary intermediates to be competitive."
1,1,2,3,2,none,no spatial aspect,single species laboratory system - no environmental aspect,gene family/microsatellites,both,Elin Videvall,2017,https://doi.org/10.1371/journal.pone.0170125,"Castronovo, G; Clemente, AM; Antonelli, A; D'Andrea, MM; Tanturli, M; Perissi, E; Paccosi, S; Parenti, A; Cozzolino, F; Rossolini, GM; Torcia, MG",Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases,PLOS ONE,12,,,e0170125,10.1371/journal.pone.0170125,"ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital -acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines. Significant differences between the strains were found in their ability to induce the production of IL-1 beta: KK207-1/clade I was much less effective than KKBO-1/clade II in inducing IL-1 beta production by monocytes and dendritic cells. The activation of NLRP3 inflammasome pathway by live cells and/or purified capsular polysaccharides was studied in monocytes and dendritic cells. We found that glibenclamide, a NLRP3 inhibitor, inhibits more than 90% of the production of mature IL-1 beta induced by KKBO1 and KK207-1. KK207-1 was always less efficient compared to KKBO-1 in: a) inducing NLRP3 and pro-IL-1 beta gene and protein expression; b) in inducing caspase-1 activation and prod L113 cleavage. Capsular composition may play a role in the differential inflammatory response induced by the ST258-KP strains since capsular polysaccharides purified from bacterial cells affect NLRP3 and pro-IL-1 beta gene expression through p38MAPK-and NF-kappa B-mediated pathways. In each of these functions, capsular polysaccharides from KK207-1 were significantly less efficient compared to those purified from KKBO-1. On the whole, our data suggest that the change in capsular phenotype may help bacterial cells of Glade Ito partially escape innate immune recognition and IL-1 beta-mediated inflammation."
1,5,1,7,6,none,global spatial scale,none - theoretical,whole genome,both,Elin Videvall,2017,https://doi.org/10.1093/nar/gkw1105,"Aurrecoechea, C; Barreto, A; Basenko, EY; Brestelli, J; Brunk, BP; Cade, S; Crouch, K; Doherty, R; Falke, D; Fischer, S; Gajria, B; Harb, OS; Heiges, M; Hertz-Fowler, C; Hu, SF; Iodice, J; Kissinger, JC; Lawrence, C; Li, W; Pinney, DF; Pulman, JA; Roos, DS; Shanmugasundram, A; Silva-Franco, F; Steinbiss, S; Stoeckert, CJ; Spruill, D; Wang, HM; Warrenfeltz, S; Zheng, J",EuPathDB: the eukaryotic pathogen genomics database resource,NUCLEIC ACIDS RESEARCH,45,D581,D591,,10.1093/nar/gkw1105,"The Eukaryotic Pathogen Genomics Database Resource (EuPathDB, http://eupathdb.org) is a collection of databases covering 170+ eukaryotic pathogens (protists & fungi), along with relevant free-living and non-pathogenic species, and select pathogen hosts. To facilitate the discovery of meaningful biological relationships, the databases couple preconfigured searches with visualization and analysis tools for comprehensive data mining via intuitive graphical interfaces and APIs. All data are analyzed with the same workflows, including creation of gene orthology profiles, so data are easily compared across data sets, data types and organisms. EuPathDB is updated with numerous new analysis tools, features, data sets and data types. New tools include GO, metabolic pathway and word enrichment analyses plus an online workspace for analysis of personal, non-public, large-scale data. Expanded data content is mostly genomic and functional genomic data while new data types include protein microarray, metabolic pathways, compounds, quantitative proteomics, copy number variation, and polysomal transcriptomics. New features include consistent categorization of searches, data sets and genome browser tracks; redesigned gene pages; effective integration of alternative transcripts; and a EuPathDB Galaxy instance for private analyses of a user's data. Forthcoming upgrades include user workspaces for private integration of data with existing EuPathDB data and improved integration and presentation of host-pathogen interactions."
1,1,2,2,2,none,no spatial aspect,single species laboratory system - no environmental aspect,full gene/regulator,Pathogen,Elin Videvall,2017,https://doi.org/10.1155/2017/6746437,"Leineweber, M; Spekker-Bosker, K; Ince, V; Schares, G; Hemphill, A; Eller, SK; Daubener, W",First Characterization of the Neospora caninum Dense Granule Protein GRA9,BIOMED RESEARCH INTERNATIONAL,NA,,,6746437,10.1155/2017/6746437,"The obligate intracellular apicomplexan parasite Neospora caninum (N. caninum) is closely related to Toxoplasma gondii (T. gondii). The dense granules, which are present in all apicomplexan parasites, are important secretory organelles. Dense granule (GRA) proteins are released into the parasitophorous vacuole (PV) following host cell invasion and are known to play important roles in themaintenance of the host-parasite relationship and in the acquisition of nutrients. Here, we provide a detailed characterization of the N. caninum dense granule protein NcGRA9. The in silico genomic organization and key protein characteristics are described. Immunofluorescence-based localization studies revealed that NcGRA9 is located in the dense granules and is released into the interior of the PV following host cell invasion. Immunogold-electron microscopy confirmed the dense granule localization and showed that NcGRA9 is associated with the intravacuolar network. In addition, NcGRA9 is found in the ""excreted secreted antigen"" (ESA) fraction of N. caninum. Furthermore, by analysing the distribution of truncated versions of NcGRA9, we provide evidence that the C-terminal region of this protein is essential for the targeting of NcGRA9 into the dense granules of N. caninum, and the truncated proteins show reduced secretion."
1,2,8,7,3,none,local (one population),multiple species in the wild - environment constant,whole genome,Pathogen,Elin Videvall,2017,https://doi.org/10.1007/978-1-4939-6691-2_7,"Doonan, J; Denman, S; McDonald, JE; Golyshin, PN",Shotgun Metagenomic Sequencing Analysis of Soft-Rot Enterobacteriaceae in Polymicrobial Communities,"METAGENOMICS: METHODS AND PROTOCOLS, 2ND EDITION",1539,85,97,,10.1007/978-1-4939-6691-2_7,"Shotgun metagenomic sequencing of bacterial communities in necrotic plant lesions allows insights of host-pathogen molecular interactions. Soft-rot Enterobacteriaceae are significant crop pathogens with a wide host range. Reconstructed polymicrobial community DNA from soft-rot affected crops provides details of species relative abundance and functional potential, enabling significant insights into their lifestyle. Here, we describe a workflow for DNA recovery, metagenomic shotgun sequencing and in particular, an in silico analysis of bacterial isolates from affected plant tissue."
1,3,2,7,4,none,small spatial scale (couple of populations),single species laboratory system - no environmental aspect,whole genome,both,Elin Videvall,2017,https://doi.org/10.2174/1389202918666170705160615,"Nammi, D; Yarla, NS; Chubarev, VN; Tarasov, VV; Barreto, GE; Pasupulati, AMC; Aliev, G; Neelapu, NRR",A Systematic in-silico Analysis of Helicobacter pylori Pathogenic Islands for Identification of Novel Drug Target Candidates,CURRENT GENOMICS,18,450,465,,10.2174/1389202918666170705160615,"Background: Helicobacter pylori is associated with inflammation of different areas, such as the duodenum and stomach, causing gastritis and gastric ulcers leading to lymphoma and cancer. Pathogenic islands are a type of clustered mobile elements ranging from 10-200 Kb contributing to the virulence of the respective pathogen coding for one or more virulence factors. Virulence factors are molecules expressed and secreted by pathogen and are responsible for causing disease in the host. Bacterial genes/virulence factors of the pathogenic islands represent a promising source for identifying novel drug targets. Objective: The study aimed at identifying novel drug targets from pathogenic islands in H. pylori. Material & Methods: The genome of 23 H. pylori strains were screened for pathogenic islands and bacterial genes/virulence factors to identify drug targets. Protein-protein interactions of drug targets were predicted for identifying interacting partners. Further, host-pathogen interactions of interacting partners were predicted to identify important molecules which are closely associated with gastric cancer. Results: Screening the genome of 23 H. pylori strains revealed 642 bacterial genes/virulence factors in 31 pathogenic islands. Further analysis identified 101 genes which were non-homologous to human and essential for the survival of the pathogen, among them 31 are potential drug targets. Proteinprotein interactions for 31 drug targets predicted 609 interacting partners. Predicted interacting partners were further subjected to host-pathogen interactions leading to identification of important molecules like TNF receptor associated factor 6, (TRAF6) and MAPKKK7 which are closely associated with gastric cancer. Conclusion: These provocative studies enabled us to identify important molecules in H. pylori and their counter interacting molecules in the host leading to gastric cancer and also a pool of novel drug targets for therapeutic intervention of gastric cancer."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Elin Videvall,2016,https://doi.org/10.3389/fpls.2016.01943,"Yadav, IS; Sharma, A; Kaur, S; Nahar, N; Bhardwaj, SC; Sharma, TR; Chhuneja, P",Comparative Temporal Transcriptome Profiling of Wheat near Isogenic Line Carrying Lr57 under Compatible and Incompatible Interactions,FRONTIERS IN PLANT SCIENCE,7,,,1943,10.3389/fpls.2016.01943,"Leaf rust caused by Puccinia triticina (Pt) is one of the most important diseases of bread wheat globally. Recent advances in sequencing technologies have provided opportunities to analyse the complete transcriptomes of the host as well as pathogen for studying differential gene expression during infection. Pathogen induced differential gene expression was characterized in a near isogenic line carrying leaf rust resistance gene Lr57 and susceptible recipient genotype VVL711. RNA samples were collected at five different time points 0, 12, 24, 48, and 72 h post inoculation (HPI) with Pt 77-5. A total of 3020 transcripts were differentially expressed with 1458 and 2692 transcripts in WL711 and WL711+Lr57, respectively. The highest number of differentially expressed transcripts was detected at 12 HPI. Functional categorization using Blast2GO classified the genes into biological processes, molecular function and cellular components. WL711+Lr57 showed much higher number of differentially expressed nucleotide binding and leucine rich repeat genes and expressed more protein kinases and pathogenesis related proteins such as chitinases, glucanases and other PR proteins as compared to susceptible genotype. Pathway annotation with KEGG categorized genes into 13 major classes with carbohydrate metabolism being the most prominent followed by amino acid, secondary metabolites, and nucleotide metabolism. Gene co-expression network analysis identified four and eight clusters of highly correlated genes in VVL711 and WL711 Lr57, respectively. Comparative analysis of the differentially expressed transcripts led to the identification of some transcripts which were specifically expressed only in VVL711 Lr57. It was apparent from the whole transcriptome sequencing that the resistance gene Lr57 directed the expression of different genes involved in building the resistance response in the host to combat invading pathogen. The RNAseq data and differentially expressed transcripts identified in present study is a genomic resource which can be used for further studying the host pathogen interaction for Lr57 and wheat transcriptome in general."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Pathogen,Emily O'Connor,2016,https://doi.org/10.1186/s12864-016-3363-1,"Hobbs, CK; Porter, VL; Stow, MLS; Siame, BA; Tsang, HH; Leung, KY",Computational approach to predict species-specific type III secretion system (T3SS) effectors using single and multiple genomes,BMC GENOMICS,17,,,1048,10.1186/s12864-016-3363-1,"Background: Many gram-negative bacteria use type III secretion systems (T3SSs) to translocate effector proteins into host cells. T3SS effectors can give some bacteria a competitive edge over others within the same environment and can help bacteria to invade the host cells and allow them to multiply rapidly within the host. Therefore, developing efficient methods to identify effectors scattered in bacterial genomes can lead to a better understanding of host-pathogen interactions and ultimately to important medical and biotechnological applications. Results: We used 21 genomic and proteomic attributes to create a precise and reliable T3SS effector prediction method called Genome Search for Effectors Tool (GenSET). Five machine learning algorithms were trained on effectors selected from different organisms and a trained (voting) algorithm was then applied to identify other effectors present in the genome testing sets from the same (GenSET Phase 1) or different (GenSET Phase 2) organism. Although a select group of attributes that included the codon adaptation index, probability of expression in inclusion bodies, N-terminal disorder, and G + C content (filtered) were better at discriminating between positive and negative sets, algorithm performance was better when all 21 attributes (unfiltered) were used. Performance scores (sensitivity, specificity and area under the curve) from GenSET Phase 1 were better than those reported for six published methods. More importantly, GenSET Phase 1 ranked more known effectors (70.3%) in the top 40 ranked proteins and predicted 10-80% more effectors than three available programs in three of the four organisms tested. GenSET Phase 2 predicted 43.8% effectors in the top 40 ranked proteins when tested on four related or unrelated organisms. The lower prediction rates from GenSET Phase 2 may be due to the presence of different translocation signals in effectors from different T3SS families. Conclusions: The species-specific GenSET Phase 1 method offers an alternative approach to T3SS effector prediction that can be used with other published programs to improve effector predictions. Additionally, our approach can be applied to predict effectors of other secretion systems as long as these effectors have translocation signals embedded in their sequences."
4,1,2,7,5,many generations,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Emily O'Connor,2016,https://doi.org/10.1139/cjm-2016-0297,"Slaine, PD; Ackford, JG; Kropinski, AM; Kozak, RA; Krell, PJ; Nagy, E",Molecular characterization of pathogenic and nonpathogenic fowl aviadenovirus serotype 11 isolates,CANADIAN JOURNAL OF MICROBIOLOGY,62,993,1002,,10.1139/cjm-2016-0297,"Fowl aviadenoviruses, many of which are of importance in veterinary medicine, are classified into 5 species. In this study, a pathogenic isolate and a nonpathogenic isolate of fowl aviadenovirus serotype 11 (FAdV-11) of species Fowl aviadenovirus D were characterized. Growth rates were analyzed for the 2 isolates, showing notable differences. The complete genomic sequences of the viruses were fully determined and were analyzed. The genomes of the 2 isolates showed 98.1% sequence identity and revealed 6 nonsynonymous mutations between the Ontario isolates. Two of the 6 mutations were also found in the sequences of recently published pathogenic Chinese fowl aviadenovirus 11 isolates, suggesting potential molecular markers that could be associated with pathogenesis. Deletions were found in the L5 region within the overlapping coding sequences for the 100, 22, and 33 kDa proteins, and these were found in only the nonpathogenic isolates. This molecular pattern was identified in FAdV-9, another nonpathogenic FAdV-D species virus. Furthermore, the tandem repeat regions varied dramatically; the pathogenic isolates contained a reduced number of tandem repeats compared with the nonpathogenic isolates. Lastly, a protein produced early in infection was analyzed using bioinformatics to determine its role in disease. This study highlights several candidate molecular determinants of avian adenovirus genomes related to pathogenicity."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Emily O'Connor,2016,https://doi.org/10.1016/j.vetmic.2016.10.015,"Bravo, C; Martinez, V",Whole-genome comparative analysis of the pathogen Piscirickettsia salmonis,VETERINARY MICROBIOLOGY,196,36,43,,10.1016/j.vetmic.2016.10.015,"The intracellular pathogen Piscirickettsia salmonis is the etiological agent of piscirickettsiosis, the most important bacterial disease that affects the Chilean salmon industry. Despite its importance, little is known regarding the biology of the pathogen. In this study, recently published sequencing data was used in order to characterize the genome of P. salmonis, defining groups of genes associated with bacterial processes such as, invasion and intracellular survival. Moreover, one Chilean P. salmonis isolate, which is known to be virulent at in vitro and in vivo assays, was sequenced, assembled, annotated and functionally characterized. Whole-genome comparisons between public P. salmonis isolates confirmed the existence of two different genogroups associated with the LF-89 and EM-90 strains, and the bacterial pan and core genome were defined. Additionally, differences were observed at the genomic level between the P. salmonis reference strain and a Norwegian isolate, which is known to produce milder piscirickettsiosis outbreaks. Finally, candidate genes for invasion and intracellular survival were chosen from phylogenetically related bacteria, and annotated in P. salmonis using comparative genomics. These results showed the presence of several genes that might be related to bacterial pathogenesis, for example those of the type III, IV and VI secretion systems, in which some amino acidic differences within both genogroups and the Norwegian isolate were established. Altogether, these results will be relevant for understanding the host-pathogen interaction and further studies, aimed at generating new disease control strategies, should be devised using this information. (C) 2016 Elsevier B.V. All rights reserved."
4,3,7,7,7,many generations,small spatial scale (couple of populations),single species in the wild - environment changing,whole genome,Pathogen,Emily O'Connor,2016,https://doi.org/10.1016/j.vetmic.2016.10.010,"Parker, AM; Shukla, A; House, JK; Hazelton, MS; Bosward, KL; Kokotovic, B; Sheehy, PA",Genetic characterization of Australian Mycoplasma bovis isolates through whole genome sequencing analysis,VETERINARY MICROBIOLOGY,196,118,125,,10.1016/j.vetmic.2016.10.010,"Mycoplasma bovis is a major pathogen in cattle causing mastitis, arthritis and pneumonia. First isolated in Australian cattle in 1970, M. bovis has persisted causing serious disease in infected herds. To date, genetic analysis of Australian M. bovis isolates has not been performed. With whole genome sequencing (WGS) becoming a common tool for genetic characterization, this method was utilized to determine the degree of genetic diversity among Australian M. bovis isolates collected over a nine year period (2006-2015) from various geographical locations, anatomical sites, and from clinically affected and non-clinical carrier animals. Eighty-two M. bovis isolates underwent WGS from which single nucleotide polymorphism (SNP) analysis, comparative genomics and analysis of virulence genes was completed. SNP analysis identified a single M. bovis strain circulating throughout Australia with marked genomic similarity. Comparative genomics suggested minimal variation in gene content between isolates from clinical and carrier animals, and between isolates recovered from different anatomical sites. A total of 50 virulence genes from the virulence factors database (VFDB) were identified as highly similar in the Australian isolates, while the presence of variable surface lipoprotein (vsp) genes was greatly reduced compared to reference strain M. bovis PG45. These results highlight that, while the introduction of multiple M. bovis strains has been prevented, elimination of the current strain has not been successful. The persistence of this strain may be due to the significant role that carrier animals play in harboring the pathogen. The similarity of clinical and non-clinical isolates suggests host and environmental factors play a significant role in determining host pathogen outcomes. (C) 2016 Elsevier B.V. All rights reserved."
5,4,9,7,9,speciation time (small tree),species range,multiple species in the wild - environment changing,whole genome,both,Emily O'Connor,2016,https://doi.org/10.3389/fmicb.2016.01759,"Forde, TL; Orsel, K; Zadoks, RN; Biek, R; Adams, LG; Checkley, SL; Davison, T; De Buck, J; Dumond, M; Elkin, BT; Finnegan, L; Macbeth, BJ; Nelson, C; Niptanatiak, A; Sather, S; Schwantje, HM; van der Meer, F; Kutz, SJ",Bacterial Genomics Reveal the Complex Epidemiology of an Emerging Pathogen in Arctic and Boreal Ungulates,FRONTIERS IN MICROBIOLOGY,7,,,1759,10.3389/fmicb.2016.01759,"Northern ecosystems are currently experiencing unprecedented ecological change, largely driven by a rapidly changing climate. Pathogen range expansion, and emergence and altered patterns of infectious disease, are increasingly reported in wildlife at high latitudes. Understanding the causes and consequences of shifting pathogen diversity and host-pathogen interactions in these ecosystems is important for wildlife conservation, and for indigenous populations that depend on wildlife. Among the key questions are whether disease events are associated with endemic or recently introduced pathogens, and whether emerging strains are spreading throughout the region. In this study, we used a phylogenomic approach to address these questions of pathogen endemicity and spread for Erysipelothrix rhusiopathiae, an opportunistic multi-host bacterial pathogen associated with recent mortalities in arctic and boreal ungulate populations in North America. We isolated E. rhusiopathiae from carcasses associated with large-scale die-offs of muskoxen in the Canadian Arctic Archipelago, and from contemporaneous mortality events and/or population declines among muskoxen in northwestern Alaska and caribou and moose in western Canada. Bacterial genomic diversity differed markedly among these locations; minimal divergence was present among isolates from muskoxen in the Canadian Arctic, while in caribou and moose populations, strains from highly divergent clades were isolated from the same location, or even from within a single carcass. These results indicate that mortalities among northern ungulates are not associated with a single emerging strain of E. rhusiopathiae, and that alternate hypotheses need to be explored. Our study illustrates the value and limitations of bacterial genomic data for discriminating between ecological hypotheses of disease emergence, and highlights the importance of studying emerging pathogens within the broader context of environmental and host factors."
5,3,8,2,8,speciation time (small tree),small spatial scale (couple of populations),multiple species in the wild - environment constant,full gene/regulator,Host,Emily O'Connor,2016,https://doi.org/10.1002/bip.22938,"da Cunha, NB; Barbosa, AEAD; de Almeida, RG; Porto, WF; Maximiano, MR; Alvares, LCS; Munhoz, CBR; Eugenio, CUO; Viana, AAB; Franco, OL; Dias, SC",Cloning and characterization of novel cyclotides genes from South American plants,BIOPOLYMERS,106,784,795,,10.1002/bip.22938,"Cyclotides are multifunctional plant cyclic peptides containing 28-37 amino acid residues and a pattern of three disulfide bridges, forming a motif known as the cyclic cystine knot. Due to their high biotechnological potential, the sequencing and characterization of cyclotide genes are crucial not only for cloning and establishing heterologous expression strategies, but also to understand local plant evolution in the context of host-pathogen relationships. Here, two species from the Brazilian Cerrado, Palicourea rigida (Rubiaceae) and Pombalia lanata (A. St.-Hil.) Paula-Souza (Violaceae), were used for cloning and characterizing novel cyclotide genes. Using 30 and 50 RACE PCR and sequencing, two full cDNAs, named parigidin-br2 (P. rigida) and hyla-br1 (P. lanata), were isolated and shown to have similar genetic structures to other cyclotides. Both contained the conserved ER-signal domain, N-terminal prodomain, mature cyclotide domain and a C-terminal region. Genomic sequencing of parigidin-br2 revealed two different gene copies: one intronless allele and one presenting a rare 131-bp intron. In contrast, genomic sequencing of hyla-br1 revealed an intronless gene-a common characteristic of members of the Violaceae family. Parigidin-br2 5' and 3' UTRs showed the presence of 12 putative candidate sites for binding of regulatory proteins, suggesting that the flanking and intronic regions of the parigidin-br2 gene must play important roles in transcriptional rates and in the regulation of temporal and spatial gene expression. The high degree of genetic similarity and structural organization among the cyclotide genes isolated in the present study from the Brazilian Cerrado and other well-characterized plant cyclotides may contribute to a better understanding of cyclotide evolution."
5,1,8,2,6,speciation time (small tree),no spatial aspect,multiple species in the wild - environment constant,full gene/regulator,Host,Emily O'Connor,2016,https://doi.org/10.1093/gbe/evw236,"Fijarczyk, A; Dudek, K; Babik, W",Selective Landscapes in newt Immune Genes Inferred from Patterns of Nucleotide Variation,GENOME BIOLOGY AND EVOLUTION,8,3417,3432,,10.1093/gbe/evw236,"Host-pathogen interactions may result in either directional selection or in pressure for the maintenance of polymorphism at the molecular level. Hence signatures of both positive and balancing selection are expected in immune genes. Because both overall selective pressure and specific targets may differ between species, large-scale population genomic studies are useful in detecting functionally important immune genes and comparing selective landscapes between taxa. Such studies are of particular interest in amphibians, a group threatened worldwide by emerging infectious diseases. Here, we present an analysis of polymorphism and divergence of 634 immune genes in two lineages of Lissotriton newts: L. montandoni and L. vulgaris graecus. Variation in newt immune genes has been shaped predominantly by widespread purifying selection and strong evolutionary constraint, implying long-term importance of these genes for functioning of the immune system. The two evolutionary lineages differ in the overall strength of purifying selection which can partially be explained by demographic history but may also signal differences in long-term pathogen pressure. The prevalent constraint notwithstanding, 23 putative targets of positive selection and 11 putative targets of balancing selection were identified. The latter were detected by composite tests involving the demographic model and further validated in independent population samples. Putative targets of balancing selection encode proteins which may interact closely with pathogens but include also regulators of immune response. The identified candidates will be useful for testing whether genes affected by balancing selection are more prone to interspecific introgression than other genes in the genome."
1,1,6,2,2,none,no spatial aspect,single species in the wild - environment constant,full gene/regulator,Pathogen,Emily O'Connor,2016,https://doi.org/10.1016/j.molbiopara.2016.08.001,"McAllaster, MR; Sinclair-Davis, AN; Hilton, NA; de Graffenried, CL",A unified approach towards Trypanosoma brucei functional genomics using Gibson assembly,MOLECULAR AND BIOCHEMICAL PARASITOLOGY,210,13,21,,10.1016/j.molbiopara.2016.08.001,"Trypanosoma brucei is the causative agent of human African trypanosomiasis and nagana in cattle. Recent advances in high throughput phenotypic and interaction screens have identified a wealth of novel candidate proteins for diverse functions such as drug resistance, life cycle progression, and cytoskeletal biogenesis. Characterization of these proteins will allow a more mechanistic understanding of the biology of this important pathogen and could identify novel drug targets. However, methods for rapidly validating and prioritizing these potential targets are still being developed. While gene tagging via homologous recombination and RNA interference are available in T. brucei, a general strategy for creating the most effective constructs for these approaches is lacking. Here, we adapt Gibson assembly, a one-step isothermal process that rapidly assembles multiple DNA segments in a single reaction, to create endogenous tagging, overexpression, and long hairpin RNAi constructs that are compatible with well-established T. brucei vectors. The generality of the Gibson approach has several advantages over current methodologies and substantially increases the speed and ease with which these constructs can be assembled. (C) 2016 Elsevier B.V. All rights reserved."
5,5,9,7,10,speciation time (small tree),global spatial scale,multiple species in the wild - environment changing,whole genome,Pathogen,Emily O'Connor,2016,https://doi.org/10.1099/mgen.0.000094,"Duchene, S; Holt, KE; Weill, FX; Le Hello, S; Hawkey, J; Edwards, DJ; Fourment, M; Holmes, EC",Genome-scale rates of evolutionary change in bacteria,MICROBIAL GENOMICS,2,,,UNSP 000094,10.1099/mgen.0.000094,"Estimating the rates at which bacterial genomes evolve is critical to understanding major evolutionary and ecological processes such as disease emergence, long-term host-pathogen associations and short-term transmission patterns. The surge in bacterial genomic data sets provides a new opportunity to estimate these rates and reveal the factors that shape bacterial evolutionary dynamics. For many organisms estimates of evolutionary rate display an inverse association with the time-scale over which the data are sampled. However, this relationship remains unexplored in bacteria due to the difficulty in estimating genome-wide evolutionary rates, which are impacted by the extent of temporal structure in the data and the prevalence of recombination. We collected 36 whole genome sequence data sets from 16 species of bacterial pathogens to systematically estimate and compare their evolutionary rates and assess the extent of temporal structure in the absence of recombination. The majority (28/36) of data sets possessed sufficient clock-like structure to robustly estimate evolutionary rates. However, in some species reliable estimates were not possible even with 'ancient DNA' data sampled over many centuries, suggesting that they evolve very slowly or that they display extensive rate variation among lineages. The robustly estimated evolutionary rates spanned several orders of magnitude, from approximately 10(-5) to 10(-8) nucleotide substitutions per site year(-1). This variation was negatively associated with sampling time, with this relationship best described by an exponential decay curve. To avoid potential estimation biases, such time-dependency should be considered when inferring evolutionary time-scales in bacteria."
5,4,7,7,9,speciation time (small tree),species range,single species in the wild - environment changing,whole genome,Pathogen,Emily O'Connor,2016,https://doi.org/10.1186/s12864-016-3185-1,"Siena, E; D'Aurizio, R; Riley, D; Tettelin, H; Guidotti, S; Torricelli, G; Moxon, ER; Medini, D",In-silico prediction and deep-DNA sequencing validation indicate phase variation in 115 Neisseria meningitidis genes,BMC GENOMICS,17,,,843,10.1186/s12864-016-3185-1,"Background: The Neisseria meningitidis (Nm) chromosome shows a high abundance of simple sequence DNA repeats (SSRs) that undergo stochastic, reversible mutations at high frequency. This mechanism is reflected in an extensive phenotypic diversity that facilitates Nm adaptation to dynamic environmental changes. To date, phase-variable phenotypes mediated by SSRs variation have been experimentally confirmed for 26 Nm genes. Results: Here we present a population-scale comparative genomic analysis that identified 277 genes and classified them into 52 strong, 60 moderate and 165 weak candidates for phase variation. Deep-coverage DNA sequencing of single colonies grown overnight under non-selective conditions confirmed the presence of high-frequency, stochastic variation in 115 of them, providing circumstantial evidence for their phase variability. We confirmed previous observations of a predominance of variable SSRs within genes for components located on the cell surface or DNA metabolism. However, in addition we identified an unexpectedly broad spectrum of other metabolic functions, and most of the variable SSRs were predicted to induce phenotypic changes by modulating gene expression at a transcriptional level or by producing different protein isoforms rather than mediating on/off translational switching through frameshifts. Investigation of the evolutionary history of SSR contingency loci revealed that these loci were inherited from a Nm ancestor, evolved independently within Nm, or were acquired by Nm through lateral DNA exchange. Conclusions: Overall, our results have identified a broader and qualitatively different phenotypic diversification of SSRs-mediated stochastic variation than previously documented, including its impact on central Nm metabolism."
4,4,7,7,8,many generations,species range,single species in the wild - environment changing,whole genome,Pathogen,Emily O'Connor,2016,https://doi.org/10.1038/srep35284,"Silva, JC; Cornillot, E; McCracken, C; Usmani-Brown, S; Dwivedi, A; Ifeonu, OO; Crabtree, J; Gotia, HT; Virji, AZ; Reynes, C; Colinge, J; Kumar, V; Lawres, L; Pazzi, JE; Pablo, JV; Hung, C; Brancato, J; Kumari, P; Orvis, J; Tretina, K; Chibucos, M; Ott, S; Sadzewicz, L; Sengamalay, N; Shetty, AC; Su, Q; Tallon, L; Fraser, CM; Frutos, R; Molina, DM; Krause, PJ; Ben Mamoun, C",Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions,SCIENTIFIC REPORTS,6,,,35284,10.1038/srep35284,"Babesia microti, a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite. Furthermore, we found that polymorphism is restricted to a small number of genes, which are highly expressed during infection. In order to identify pathogen-encoded factors involved in host-parasite interactions, we screened a proteome array comprised of 174 B. microti proteins, including several predicted members of the parasite secretome. Using this immuno-proteomic approach we identified several novel antigens that trigger strong host immune responses during the onset of infection. The genomic and immunological data presented herein provide the first insights into the determinants of B. microti interaction with its mammalian hosts and their relevance for understanding the selective pressures acting on parasite evolution."
2,1,3,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,Host,Emily O'Connor,2016,https://doi.org/10.1016/j.chom.2016.09.005,"Talmi-Frank, D; Altboum, Z; Solomonov, I; Udi, Y; Jaitin, DA; Klepfish, M; David, E; Zhuravlev, A; Keren-Shaul, H; Winter, DR; Gat-Viks, I; Mandelboim, M; Ziv, T; Amit, I; Sagi, I",Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality,Cell Host & Microbe,20,458,470,,10.1016/j.chom.2016.09.005,"Mounting an effective immune response, while also protecting tissue integrity, is critical for host survival. We used a combined genomic and proteomic approach to investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection. We identified the membrane-tethered matrix metalloprotease MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza infection. Selective inhibition of MT1-MMP protected the tissue from infection-related structural and compositional tissue damage. MT1-MMP inhibition did not significantly alter the immune response or cytokine expression. The available flu therapeutic Oseltamivir did not prevent lung ECM damage and was less effective than anti-MT1-MMP in influenza virus Streptococcus pneumoniae coinfection paradigms. Combination therapy of Oseltamivir with anti-MT1-MMP showed a strong synergistic effect and resulted in complete recovery of infected mice. This study highlights the importance of tissue resilience in surviving infection and the potential of such host-pathogen therapy combinations for respiratory infections."
5,4,7,5,9,speciation time (small tree),species range,single species in the wild - environment changing,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Pathogen,Emily O'Connor,2016,https://doi.org/10.1111/1758-2229.12431,"Gonzalez-Barrio, D; Jado, I; Fernandez-de-Mera, IG; Fernandez-Santos, MD; Rodriguez-Vargas, M; Garcia-Amil, C; Beltran-Beck, B; Anda, P; Ruiz-Fons, F",Genotypes of Coxiella burnetii in wildlife: disentangling the molecular epidemiology of a multi-host pathogen,ENVIRONMENTAL MICROBIOLOGY REPORTS,8,708,714,,10.1111/1758-2229.12431,"Evidences point to a relevant role of wildlife in the ecology of Coxiella burnetii worldwide. The lack of information on C. burnetii genotypes in wildlife prevents tracing-back clinical animal and human Q fever cases with potential wildlife origin. To compare C. burnetii genotypes circulating in wildlife, livestock and humans, 107 samples from red deer, European wild rabbit, racoon, small mammals, goat and sheep were genotyped by polymerase chain reaction and reverse line blot hybridization. Genomic groups I, II, VI and VII were found in wildlife and groups I, II, III and IV in domestic ruminants. Livestock genotypes clustered mainly with genotypes reported previously in livestock. Genotyping confirmed previous findings that suggest that C. burnetii may display host specificity since most genotypes of sympatric deer and rabbits clustered in separate groups. Wildlife genotypes clustered with genotypes from ticks and from acute hepatitis human Q fever cases, suggesting that particular C. burnetii genotypes circulating in a wildlife-tick cycle may occasionally jump into humans through tick bites or exposure to wildlife. This finding could be behind the reported geographic variation in the clinical presentation of acute Q fever in humans in Spain: atypical pneumonia in the north and hepatitis in the south."
1,1,6,4,2,none,no spatial aspect,single species in the wild - environment constant,"whole plastid genome (mtDNA, apiDNA)",Pathogen,Emily O'Connor,2016,https://doi.org/10.1093/aob/mcw135,"Roquet, C; Coissac, E; Cruaud, C; Boleda, M; Boyer, F; Alberti, A; Gielly, L; Taberlet, P; Thuiller, W; Van Es, J; Lavergne, S",Understanding the evolution of holoparasitic plants: the complete plastid genome of the holoparasite Cytinus hypocistis (Cytinaceae),ANNALS OF BOTANY,118,885,896,,10.1093/aob/mcw135,"Background and Aims Plant plastid genomes are highly conserved in size, gene content and structure; however, parasitic plants are a noticeable exception to this evolutionary stability. Although the evolution of parasites could help to better understand plastome evolution in general, complete plastomes of parasites have been sequenced only for some lineages so far. Here we contribute to filling this gap by providing and analysing the complete plastome sequence of Cytinus hypocistis, the first parasite sequenced for Malvales and a species suspected to have an extremely small genome. Methods We sequenced and assembled de novo the plastid genome of Cytinus hypocistis using a shotgun approach on genomic DNA. Phylogenomic analyses based on coding regions were performed on Malvidae. For each coding region present in Cytinus, we tested for relaxation or intensification of selective pressures in the Cytinus lineage compared with autotrophic Malvales. Key Results Cytinus hypocistis has an extremely divergent genome that is among the smallest sequenced to date (19.4 kb), with only 23 genes and no inverted repeat regions. Phylogenomic analysis confirmed the position of Cytinus within Malvales. All coding regions of Cytinus plastome presented very high substitution rates compared with non-parasitic Malvales. Conclusions Some regions were inferred to be under relaxed negative selection in Cytinus, suggesting that further plastome reduction is occurring due to relaxed purifying selection associated with the loss of photosynthetic activity. On the other hand, increased selection intensity and strong positive selection were detected for rpl22 in the Cytinus lineage, which might indicate an evolutionary role in the host-parasite arms race, a point that needs further research."
4,3,7,3,7,many generations,small spatial scale (couple of populations),single species in the wild - environment changing,gene family/microsatellites,both,Emily O'Connor,2016,https://doi.org/10.1111/bij.12826,"Strobel, HM; Alda, F; Sprehn, CG; Blum, MJ; Heins, DC",Geographic and host-mediated population genetic structure in a cestode parasite of the three-spined stickleback,BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY,119,381,396,,10.1111/bij.12826,"Comparative studies of genetic diversity and population structure can shed light on the ecological and evolutionary factors that influence host-parasite interactions. Here we examined whether geography, time and genetic variation in Alaskan three-spined stickleback (Gasterosteus aculeatus Linneaus) hosts shape the population genetic structure of the diphyllobothridean cestode parasite Schistocephalus solidus (Muller, 1776). Host lineages and haplotypes were identified by sequencing the mitochondrial cytochrome b gene, and host population structure was assessed by Bayesian clustering analysis of allelic variation at 11 microsatellite loci. Parasite population structure was characterized according to allelic variation at eight microsatellite loci. Mantel tests and canonical redundancy analysis were conducted to evaluate the proportion of parasite genetic variation attributable to time and geography vs. host lineage, haplotype, and genotypic cluster. Host and parasite population structure were largely discordant across the study area, probably reflecting differences in gene flow, environmental influences external to the host, and genomic admixture among host lineages. We found that geography explained the greatest proportion of parasite genetic variation, but that variation also reflects time, host lineage, and host haplotype. Associations with host haplotypes suggest that one parasite genotypic cluster exhibits a narrower host range, predominantly infecting the most common host haplotypes, whereas the other parasite cluster infects all haplotypes equally, including rare haplotypes. Although experimental infection trials might prove otherwise, distributional differences in hosts preferentially infected by S. solidus could underlie the observed pattern of population structure. (c) 2016 The Linnean Society of London, Biological Journal of the Linnean Society, 2016, 119, 381-396."
2,1,3,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,Host,Emily O'Connor,2016,https://doi.org/10.1371/journal.pntd.0005069,"Etebari, K; Asad, S; Zhang, GM; Asgari, S",Identification of Aedes aegypti Long Intergenic Non-coding RNAs and Their Association with Wolbachia and Dengue Virus Infection,PLOS NEGLECTED TROPICAL DISEASES,10,,,e0005069,10.1371/journal.pntd.0005069,"Long intergenic non-coding RNAs (lincRNAs) are appearing as an important class of regulatory RNAs with a variety of biological functions. The aim of this study was to identify the lincRNA profile in the dengue vector Aedes aegypti and evaluate their potential role in host-pathogen interaction. The majority of previous RNA-Seq transcriptome studies in Ae. aegypti have focused on the expression pattern of annotated protein coding genes under different biological conditions. Here, we used 35 publically available RNA-Seq datasets with relatively high depth to screen the Ae. aegypti genome for lincRNA discovery. This led to the identification of 3,482 putative lincRNAs. These lincRNA genes displayed a slightly lower GC content and shorter transcript lengths compared to protein-encoding genes. Ae. aegypti lincRNAs also demonstrate low evolutionary sequence conservation even among closely related species such as Culex quinquefasciatus and Anopheles gambiae. We examined their expression in dengue virus serotype 2 (DENV-2) and Wolbachia infected and non-infected adult mosquitoes and Aa20 cells. The results revealed that DENV-2 infection increased the abundance of a number of host lincRNAs, from which some suppress viral replication in mosquito cells. RNAi-mediated silencing of lincRNA_1317 led to enhancement in viral replication, which possibly indicates its potential involvement in the host anti-viral defense. A number of lincRNAs were also differentially expressed in Wolbachia-infected mosquitoes. The results will facilitate future studies to unravel the function of lncRNAs in insects and may prove to be beneficial in developing new ways to control vectors or inhibit replication of viruses in them."
3,1,3,7,4,few generations,no spatial aspect,single species laboratory system - environmental aspect present,whole genome,Host,Emily O'Connor,2016,https://doi.org/10.1111/mec.13769,"Cogni, R; Cao, C; Day, JP; Bridson, C; Jiggins, FM",The genetic architecture of resistance to virus infection in Drosophila,MOLECULAR ECOLOGY,25,5228,5241,,10.1111/mec.13769,"Variation in susceptibility to infection has a substantial genetic component in natural populations, and it has been argued that selection by pathogens may result in it having a simpler genetic architecture than many other quantitative traits. This is important as models of host-pathogen co-evolution typically assume resistance is controlled by a small number of genes. Using the Drosophila melanogaster multiparent advanced intercross, we investigated the genetic architecture of resistance to two naturally occurring viruses, the sigma virus and DCV (Drosophila C virus). We found extensive genetic variation in resistance to both viruses. For DCV resistance, this variation is largely caused by two major-effect loci. Sigma virus resistance involves more genes - we mapped five loci, and together these explained less than half the genetic variance. Nonetheless, several of these had a large effect on resistance. Models of co-evolution typically assume strong epistatic interactions between polymorphisms controlling resistance, but we were only able to detect one locus that altered the effect of the main effect loci we had mapped. Most of the loci we mapped were probably at an intermediate frequency in natural populations. Overall, our results are consistent with major-effect genes commonly affecting susceptibility to infectious diseases, with DCV resistance being a near-Mendelian trait."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Emily O'Connor,2016,https://doi.org/10.3389/fmicb.2016.01557,"Suarez-Esquivel, M; Ruiz-Villalobos, N; Castillo-Zeledon, A; Jimenez-Rojas, C; Roop, RM; Comerci, DJ; Barquero-Calvo, E; Chacon-Diaz, C; Caswell, CC; Baker, KS; Chaves-Olarte, E; Thomson, NR; Moreno, E; Letesson, JJ; De Bolle, X; Guzman-Verri, C",Brucella abortus Strain 2308 Wisconsin Genome: Importance of the Definition of Reference Strains,FRONTIERS IN MICROBIOLOGY,7,,,1557,10.3389/fmicb.2016.01557,"Brucellosis is a bacterial infectious disease affecting a wide range of mammals and a neglected zoonosis caused by species of the genetically homogenous genus Brucella. As in most studies on bacterial diseases, research in brucellosis is carried out by using reference strains as canonical models to understand the mechanisms underlying host pathogen interactions. We performed whole genome sequencing analysis of the reference strain B. abortus 2308 routinely used in our laboratory, including manual curated annotation accessible as an editable version through a link at https://en.wikipedia.org/wiki/Brucella#Genomics. Comparison of this genome with two publically available 2308 genomes showed significant differences, particularly indels related to insertional elements, suggesting variability related to the transposition of these elements within the same strain. Considering the outcome of high resolution genomic techniques in the bacteriology field, the conventional concept of strain definition needs to be revised."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Morten Olsen,2016,https://doi.org/10.1038/srep34164,"Arnold, N; Girke, T; Sureshchandra, S; Nguyen, C; Rais, M; Messaoudi, I",Genomic and functional analysis of the host response to acute simian varicella infection in the lung,SCIENTIFIC REPORTS,6,,,34164,10.1038/srep34164,"Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development. This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair. These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host."
3,1,4,1,4,few generations,no spatial aspect,multiple species laboratory system - no environmental aspect present,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Host,Morten Olsen,2016,https://doi.org/10.1038/NPLANTS.2016.110,"MacQueen, A; Sun, XQ; Bergelson, J",Genetic architecture and pleiotropy shape costs of Rps2-mediated resistance in Arabidopsis thaliana,NATURE PLANTS,2,,,16110,10.1038/NPLANTS.2016.110,"The mounting evidence that R genes incur large fitness costs raises a question: how can there be a 5-10% fitness reduction for all 149 R genes in the Arabidopsis thaliana genome? The R genes tested to date segregate for insertion-deletion (indel) polymorphisms where susceptible alleles are complete deletions. Since costs of resistance are measured as the differential fitness of isolines carrying resistant and susceptible alleles, indels reveal costs that may be masked when susceptible alleles are expressed. Rps2 segregates for two expressed clades of alleles, one resistant and one susceptible. Plants with resistant Rps2 are not less fit than those with a susceptible Rps2 allele in the absence of disease. Instead, all alleles provide a fitness benefit relative to an artificial deletion because of the role of RPS2 as a negative regulator of defence. Our results highlight the interplay between genomic architecture and the magnitude of costs of resistance."
3,1,6,1,4,few generations,no spatial aspect,single species in the wild - environment constant,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Morten Olsen,2016,https://doi.org/10.1016/j.zool.2016.04.003,"Gonzalez-Tortuero, E; Rusek, J; Turko, P; Petrusek, A; Maayan, I; Pialek, L; Tellenbach, C; Giessler, S; Spaak, P; Wolinska, J",Daphnia parasite dynamics across multiple Caullerya epidemics indicate selection against common parasite genotypes,ZOOLOGY,119,314,321,,10.1016/j.zool.2016.04.003,"Studies of parasite population dynamics in natural systems are crucial for our understanding of host-parasite coevolutionary processes. Some field studies have reported that host genotype frequencies in natural populations change over time according to parasite-driven negative frequency -dependent selection. However, the temporal patterns of parasite genotypes have rarely been investigated. Moreover, parasite-driven negative frequency -dependent selection is contingent on the existence of genetic specificity between hosts and parasites. In the present study, the population dynamics and host-genotype specificity of the ichthyosporean Caullerya mesnili, a common endoparasite of Daphnia water fleas, were analysed based on the observed sequence variation in the first internal transcribed spacer (ITS1) of the ribosomal DNA. The Daphnia population of lake Greifensee (Switzerland) was sampled and subjected to parasite screening and host genotyping during C. mesnili epidemics of four consecutive years. The ITS1 of wild-caught C. mesnili-infected Daphnia was sequenced using the 454 pyrosequencing platform. The relative frequencies of C mesnili ITS1 sequences differed significantly among years: the most abundant C. mesnili ITS1 sequence decreased and rare sequences increased over the course of the study, a pattern consistent with negative frequency -dependent selection. However, only a weak signal of host -genotype specificity between C mesnili and Daphnia genotypes was detected. Use of cutting edge genomic techniques will allow further investigation of the underlying micro-evolutionary relationships within the Daphnia-C. mesnili system. (C) 2016 The Authors. Published by Elsevier GmbH."
2,1,2,2,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,full gene/regulator,Pathogen,Morten Olsen,2016,https://doi.org/10.1093/infdis/jiw139,"Bhattacharya, S; Mukherjee, O; Mukhopadhyay, AK; Chowdhury, R","A Conserved Helicobacter pylori Gene, HP0102, Is Induced Upon Contact With Gastric Cells and Has Multiple Roles in Pathogenicity",JOURNAL OF INFECTIOUS DISEASES,214,196,204,,10.1093/infdis/jiw139,"Contact with host cells is recognized as a signal capable of triggering expression of bacterial genes important for host pathogen interaction. Adherence of Helicobacter pylori to the gastric epithelial cell line AGS strongly upregulated expression of a gene, HP0102, in the adhered bacteria in all strains examined, including several Indian clinical isolates. The gene is highly conserved and ubiquitously present in all 69 sequenced H. pylori genomes at the same genomic locus, as well as in 15 Indian clinical isolates. The gene is associated with 2 distinct phenotypes related to pathogenicity. In AGS cell-adhered H. pylori, it has a role in upregulation of cagA expression from a specific sigma(28)-RNAP promoter and consequent induction of the hummingbird phenotype in the infected AGS cells. Furthermore, HP0102 has a role in chemotaxis and a Delta HP0102 mutant exhibited low acid-escape response that might account for the poor colonization efficiency of the mutant."
2,1,4,6,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - no environmental aspect present,exome/transcriptome,both,Morten Olsen,2016,https://doi.org/10.3389/fpls.2016.00925,"Guo, L; Allen, KS; Deiulio, G; Zhang, Y; Madeiras, AM; Wick, RL; Ma, LJ",A De Novo-Assembly Based Data Analysis Pipeline for Plant Obligate Parasite Metatranscriptomic Studies,FRONTIERS IN PLANT SCIENCE,7,,,925,10.3389/fpls.2016.00925,"Current and emerging plant diseases caused by obligate parasitic microbes such as rusts, downy mildews, and powdery mildews threaten worldwide crop production and food safety. These obligate parasites are typically unculturable in the laboratory, posing technical challenges to characterize them at the genetic and genomic level. Here we have developed a data analysis pipeline integrating several bioinformatic software programs. This pipeline facilitates rapid gene discovery and expression analysis of a plant host and its obligate parasite simultaneously by next generation sequencing of mixed host and pathogen RNA (i.e., metatranscriptomics). We applied this pipeline to metatranscriptomic sequencing data of sweet basil (Ocimum basilicum) and its obligate downy mildew parasite Peronospora belbahrii, both lacking a sequenced genome. Even with a single data point, we were able to identify both candidate host defense genes and pathogen virulence genes that are highly expressed during infection. This demonstrates the power of this pipeline for identifying genes important in hostpathogen interactions without prior genomic information for either the plant host or the obligate biotrophic pathogen. The simplicity of this pipeline makes it accessible to researchers with limited computational skills and applicable to metatranscriptomic data analysis in a wide range of plant-obligate-parasite systems."
4,4,6,7,8,many generations,species range,single species in the wild - environment constant,whole genome,Pathogen,Morten Olsen,2016,https://doi.org/10.1371/journal.ppat.1005759,"Walter, KS; Carpi, G; Evans, BR; Caccone, A; Diuk-Wasser, MA",Vectors as Epidemiological Sentinels: Patterns of Within-Tick Borrelia burgdorferi Diversity,PLOS PATHOGENS,12,,,e1005759,10.1371/journal.ppat.1005759,"Hosts including humans, other vertebrates, and arthropods, are frequently infected with heterogeneous populations of pathogens. Within-host pathogen diversity has major implications for human health, epidemiology, and pathogen evolution. However, pathogen diversity within-hosts is difficult to characterize and little is known about the levels and sources of within-host diversity maintained in natural populations of disease vectors. Here, we examine genomic variation of the Lyme disease bacteria, Borrelia burgdorferi (Bb), in 98 individual field-collected tick vectors as a model for study of within-host processes. Deep population sequencing reveals extensive and previously undocumented levels of Bb variation: the majority (similar to 70%) of ticks harbor mixed strain infections, which we define as levels Bb diversity pre-existing in a diverse inoculum. Within-tick diversity is thus a sample of the variation present within vertebrate hosts. Within individual ticks, we detect signatures of positive selection. Genes most commonly under positive selection across ticks include those involved in dissemination in vertebrate hosts and evasion of the vertebrate immune complement. By focusing on tick-borne Bb, we show that vectors can serve as epidemiological and evolutionary sentinels: within-vector pathogen diversity can be a useful and unbiased way to survey circulating pathogen diversity and identify evolutionary processes occurring in natural transmission cycles."
1,1,4,7,2,none,no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Host,Morten Olsen,2016,https://doi.org/10.1534/g3.116.028902,"Richards, J; Chao, SM; Friesen, T; Brueggeman, R",Fine Mapping of the Barley Chromosome 6H Net Form Net Blotch Susceptibility Locus,G3-GENES GENOMES GENETICS,6,1809,1818,,10.1534/g3.116.028902,"Net form net blotch, caused by the necrotrophic fungal pathogen Pyrenophora teres f. teres, is a destructive foliar disease of barley with the potential to cause significant yield loss in major production regions throughout the world. The complexity of the host-parasite genetic interactions in this pathosystem hinders the deployment of effective resistance in barley cultivars, warranting a deeper understanding of the interactions. Here, we report on the high-resolution mapping of the dominant susceptibility locus near the centromere of chromosome 6H in the barley cultivars Rika and Kombar, which are putatively targeted by necrotrophic effectors from P. teres f. teres isolates 6A and 15A, respectively. Utilization of progeny isolates derived from a cross of P. teres f. teres isolates 6A x 15A harboring single major virulence loci ( VK1, VK2, and VR2) allowed for the Mendelization of single inverse gene-for-gene interactions in a high-resolution population consisting of 2976 Rika x Kombar recombinant gametes. Brachypodium distachyon synteny was exploited to develop and saturate the susceptibility region with markers, delimiting it to similar to 0.24 cM and a partial physical map was constructed. This genetic and physical characterization further resolved the dominant susceptibility locus, designated Spt1 ( susceptibility to P. teres f. teres). The high-resolution mapping and cosegregation of the Spt1.R and Spt1.K gene/s indicates tightly linked genes in repulsion or alleles possibly targeted by different necrotrophic effectors. Newly developed barley genomic resources greatly enhance the efficiency of positional cloning efforts in barley, as demonstrated by the Spt1 fine mapping and physical contig identification reported here."
2,1,4,6,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - no environmental aspect present,exome/transcriptome,both,Morten Olsen,2016,https://doi.org/10.1016/j.virusres.2015.09.006,"Gerold, G; Bruening, J; Pietschmann, T",Decoding protein networks during virus entry by quantitative proteomics,VIRUS RESEARCH,218,25,39,,10.1016/j.virusres.2015.09.006,"Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins. Particularly, protein-protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake. These interactions are dynamic and frequently involve multiprotein complexes. In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox. Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques. We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future. (C) 2015 The Authors. Published by Elsevier B.V."
4,5,6,7,9,many generations,global spatial scale,single species in the wild - environment constant,whole genome,Pathogen,Morten Olsen,2016,https://doi.org/10.1186/s12864-016-2643-0,"Forde, T; Biek, R; Zadoks, R; Workentine, ML; De Buck, J; Kutz, S; Opriessnig, T; Trewby, H; van der Meer, F; Orsel, K",Genomic analysis of the multi-host pathogen Erysipelothrix rhusiopathiae reveals extensive recombination as well as the existence of three generalist clades with wide geographic distribution,BMC GENOMICS,17,,,461,10.1186/s12864-016-2643-0,"Background: Knowledge about how bacterial populations are structured is an important prerequisite for studying their ecology and evolutionary history and facilitates inquiry into host specificity, pathogenicity, geographic dispersal and molecular epidemiology. Erysipelothrix rhusiopathiae is an opportunistic pathogen that is currently reemerging in both the swine and poultry industries globally. This bacterium sporadically causes mortalities in captive marine mammals, and has recently been implicated in large-scale wildlife die-offs. However, despite its economic relevance and broad geographic and host distribution, including zoonotic potential, the global diversity, recombination rates, and population structure of this bacterium remain poorly characterized. In this study, we conducted a broad-scale genomic comparison of E. rhusiopathiae based on a diverse collection of isolates in order to address these knowledge gaps. Results: Eighty-three E. rhusiopathiae isolates from a range of host species and geographic origins, isolated between 1958 and 2014, were sequenced and assembled using both reference-based mapping and de novo assembly. We found that a high proportion of the core genome (58 %) had undergone recombination. Therefore, we used three independent methods robust to the presence of recombination to define the population structure of this species: a phylogenetic tree based on a set of conserved protein sequences, in silico chromosome painting, and network analysis. All three methods were broadly concordant and supported the existence of three distinct clades within the species E. rhusiopathiae. Although we found some evidence of host and geographical clustering, each clade included isolates from diverse host species and from multiple continents. Conclusions: Using whole genome sequence data, we confirm recent suggestions that E. rhusiopathiae is a weakly clonal species that has been shaped extensively by homologous recombination. Despite frequent recombination, we can reliably identify three distinct clades that do not clearly segregate by host species or geographic origin. Our results provide an essential baseline for future molecular epidemiological, ecological and evolutionary studies of E. rhusiopathiae and facilitate comparisons to other recombinogenic, multi-host bacteria."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Morten Olsen,2016,https://doi.org/10.1186/s13742-016-0128-3,"Hebert, FO; Grambauer, S; Barber, I; Landry, CR; Aubin-Horth, N","Transcriptome sequences spanning key developmental states as a resource for the study of the cestode Schistocephalus solidus, a threespine stickleback parasite",GIGASCIENCE,5,,,24,10.1186/s13742-016-0128-3,"Background: Schistocephalus solidus is a well-established model organism for studying the complex life cycle of cestodes and the mechanisms underlying host-parasite interactions. However, very few large-scale genetic resources for this species are available. We have sequenced and de novo-assembled the transcriptome of S. solidus using tissues from whole worms at three key developmental states - non-infective plerocercoid, infective plerocercoid and adult plerocercoid - to provide a resource for studying the evolution of complex life cycles and, more specifically, how parasites modulate their interactions with their hosts during development. Findings: The de novo transcriptome assembly reconstructed the coding sequence of 10,285 high-confidence unigenes from which 24,765 non-redundant transcripts were derived. 7,920 (77 %) of these unigenes were annotated with a protein name and 7,323 (71 %) were assigned at least one Gene Ontology term. Our raw transcriptome assembly (unfiltered transcripts) covers 92 % of the predicted transcriptome derived from the S. solidus draft genome assembly currently available on WormBase. It also provides new ecological information and orthology relationships to further annotate the current WormBase transcriptome and genome. Conclusion: This large-scale transcriptomic dataset provides a foundation for studies on how parasitic species with complex life cycles modulate their response to changes in biotic and abiotic conditions experienced inside their various hosts, which is a fundamental objective of parasitology. Furthermore, this resource will help in the validation of the S solidus gene features that have been predicted based on genomic sequence."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Morten Olsen,2016,https://doi.org/10.1186/s12866-016-0700-0,"Kumar, A; Thotakura, PL; Tiwary, BK; Krishna, R",Target identification in Fusobacterium nucleatum by subtractive genomics approach and enrichment analysis of host-pathogen protein-protein interactions,BMC MICROBIOLOGY,16,,,84,10.1186/s12866-016-0700-0,"Background: Fusobacterium nucleatum, a well studied bacterium in periodontal diseases, appendicitis, gingivitis, osteomyelitis and pregnancy complications has recently gained attention due to its association with colorectal cancer (CRC) progression. Treatment with berberine was shown to reverse F. nucleatum-induced CRC progression in mice by balancing the growth of opportunistic pathogens in tumor microenvironment. Intestinal microbiota imbalance and the infections caused by F. nucleatum might be regulated by therapeutic intervention. Hence, we aimed to predict drug target proteins in F. nucleatum, through subtractive genomics approach and host-pathogen protein-protein interactions (HP-PPIs). We also carried out enrichment analysis of host interacting partners to hypothesize the possible mechanisms involved in CRC progression due to F. nucleatum. Results: In subtractive genomics approach, the essential, virulence and resistance related proteins were retrieved from RefSeq proteome of F. nucleatum by searching against Database of Essential Genes (DEG), Virulence Factor Database (VFDB) and Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT) tool respectively. A subsequent hierarchical screening to identify non-human homologous, metabolic pathway-independent/pathway-specific and druggable proteins resulted in eight pathway-independent and 27 pathway-specific druggable targets. Co-aggregation of F. nucleatum with host induces proinflammatory gene expression thereby potentiates tumorigenesis. Hence, proteins from IBDsite, a database for inflammatory bowel disease (IBD) research and those involved in colorectal adenocarcinoma as interpreted from The Cancer Genome Atlas (TCGA) were retrieved to predict drug targets based on HP-PPIs with F. nucleatum proteome. Prediction of HP-PPIs exhibited 186 interactions contributed by 103 host and 76 bacterial proteins. Bacterial interacting partners were accounted as putative targets. And enrichment analysis of host interacting partners showed statistically enriched terms that were in positive correlation with CRC, atherosclerosis, cardiovascular, osteoporosis, Alzheimer's and other diseases. Conclusion: Subtractive genomics analysis provided a set of target proteins suggested to be indispensable for survival and pathogenicity of F. nucleatum. These target proteins might be considered for designing potent inhibitors to abrogate F. nucleatum infections. From enrichment analysis, it was hypothesized that F. nucleatum infection might enhance CRC progression by simultaneously regulating multiple signaling cascades which could lead to up-regulation of proinflammatory responses, oncogenes, modulation of host immune defense mechanism and suppression of DNA repair system."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,both,Morten Olsen,2016,https://doi.org/10.1186/s13059-016-0955-7,"Mott, GA; Thakur, S; Smakowska, E; Wang, PW; Belkhadir, Y; Desveaux, D; Guttman, DS",Genomic screens identify a new phytobacterial microbe-associated molecular pattern and the cognate Arabidopsis receptor-like kinase that mediates its immune elicitation,GENOME BIOLOGY,17,,,98,10.1186/s13059-016-0955-7,"Background: The recognition of microbe-associated molecular patterns during infection is central to the mounting of an effective immune response. In spite of their importance, it remains difficult to identify these molecules and the host receptors required for their perception, ultimately limiting our understanding of the role of these molecules in the evolution of host-pathogen relationships. Results: We employ a comparative genomics screen to identify six new immune eliciting peptides from the phytopathogenic bacterium Pseudomonas syringae. We then perform a reverse genetic screen to identify Arabidopsis thaliana leucine-rich repeat receptor-like kinases required for the recognition of these elicitors. We test the six elicitors on 187 receptor-like kinase knock-down insertion lines using a high-throughput peroxidase-based immune assay and identify multiple lines that show decreased immune responses to specific peptides. From this primary screen data, we focused on the interaction between the xup25 peptide from a bacterial xanthine/uracil permease and the Arabidopsis receptor-like kinase xanthine/uracil permease sensing 1; a family XII protein closely related to two well-characterized receptor-like kinases. We show that xup25 treatment increases pathogenesis-related gene induction, callose deposition, seedling growth inhibition, and resistance to virulent bacteria, all in a xanthine/uracil permease sensing 1-dependent manner. Finally, we show that this kinase-like receptor can bind the xup25 peptide directly. These results identify xup25 as a P. syringae microbe-associated molecular pattern and xanthine/uracil permease sensing 1 as a receptor-like kinase that detects the xup25 epitope to activate immune responses. Conclusions: The present study demonstrates an efficient method to identify immune elicitors and the plant receptors responsible for their perception. Further exploration of these molecules will increase our understanding of plant-pathogen interactions and the basis for host specificity."
2,1,4,7,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,both,Morten Olsen,2016,https://doi.org/10.1093/jme/tjv252,"Temeyer, KB; Tuckow, AP",Tick Salivary Cholinesterase: A Probable Immunomodulator of Host-parasite Interactions,JOURNAL OF MEDICAL ENTOMOLOGY,53,500,504,,10.1093/jme/tjv252,"The southern cattle tick, Rhipicephalus (Boophilus) microplus (Canestrini), is the most economically important cattle ectoparasite in the world. Rhipicephalus microplus and Rhipicephalus annulatus (Say) continue to threaten U.S. cattle producers despite eradication and an importation barrier based on inspection, dipping of imported cattle in organophosphate (OP) acaricide, and quarantine of infested premises. OP acaricides inhibit acetylcholinesterase (AChE), essential to tick central nervous system function. Unlike vertebrates, ticks possess at least three genes encoding AChEs, differing in amino acid sequence and biochemical properties. Genomic analyses of R. microplus and the related tick, Ixodes scapularis, suggest that ticks contain many genes encoding different AChEs. This work is the first report of a salivary cholinesterase (ChE) activity in R. microplus, and discusses complexity of the cholinergic system in ticks and significance of tick salivary ChE at the tick-host interface. It further provides three hypotheses that the salivary ChE plausibly functions 1) to reduce presence of potentially toxic acetylcholine present in the large bloodmeal imbibed during rapid engorgement, 2) to modulate the immune response (innate and/or acquired) of the host to tick antigens, and 3) to influence transmission and establishment of pathogens within the host animal. Ticks are vectors for a greater number and variety of pathogens than any other parasite, and are second only to mosquitoes (owing to malaria) as vectors of serious human disease. Saliva-assisted transmission (SAT) of pathogens is well-known; however, the salivary components participating in the SAT process remain to be elucidated."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Morten Olsen,2016,https://doi.org/10.1016/j.jip.2016.01.002,"Rao, R; Bhassu, S; Bing, RZY; Alinejad, T; Hassan, SS; Wang, J",A transcriptome study on Macrobrachium rosenbergii hepatopancreas experimentally challenged with white spot syndrome virus (WSSV),JOURNAL OF INVERTEBRATE PATHOLOGY,136,10,22,,10.1016/j.jip.2016.01.002,"The world production of shrimp such as the Malaysian giant freshwater prawn, Macrobrachium rosenbergii is seriously affected by the white spot syndrome virus (WSSV). There is an urgent need to understand the host pathogen interaction between M. rosenbergii and WSSV which will be able to provide a solution in controlling the spread of this infectious disease and lastly save the aquaculture industry. Now, using Next Generation Sequencing (NGS), we will be able to capture the response of the M. rosenbergii to the pathogen and have a better understanding of the host defence mechanism. Two cDNA libraries, one of WSSV-challenged M. rosenbergii and a normal control one, were sequenced using the Illumina HiSeq (TM) 2000 platform. After de novo assembly and clustering of the unigenes from both libraries, 63,584 standard unigenes were generated with a mean size of 698 bp and an N50 of 1137 bp. We successfully annotated 35.31% of all unigenes by using BLASTX program (E-value <10-5) against NCBI non redundant (Nr), Swiss-Prot, Kyoto Encyclopedia of Genes and Genome pathway (KEGG) and Orthologous Groups of proteins (COG) databases. Gene Ontology (GO) assessment was conducted using BLAST2GO software. Differentially expressed genes (DEGs) by using the FPKM method showed 8443 host genes were significantly up-regulated whereas 5973 genes were significantly down-regulated. The differentially expressed immune related genes were grouped into 15 animal immune functions. The present study showed that WSSV infection has a significant impact on the transcriptome profile of M. rosenbergii's hepatopancreas, and further enhanced the knowledge of this host-virus interaction. Furthermore, the high number of transcripts generated in this study will provide a platform for future genomic research on freshwater prawns. (C) 2016 Elsevier Inc. All rights reserved."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Jacob Roved,2016,https://doi.org/10.1016/j.fsi.2016.02.032,"Zhao, C; Fu, MJ; Wang, CY; Jiao, ZY; Qiu, LH",RNA-Seq analysis of immune-relevant genes in Lateolabrax japonicus during Vibrio anguillarum infection,FISH & SHELLFISH IMMUNOLOGY,52,57,64,,10.1016/j.fsi.2016.02.032,"Lateolabrax japonicus is one of the main marine aquatic fish species, and is popularly cultured in East Asia due to its highly commercial value. In recent years, because of large-scale and intensive farming and seawater pollution, fish diseases keep breaking out. However, systematic study on L. japonicus immunogenetics is limited due to the deficiency of deep sequencing technologies and genome backgrounds. In this study, the widely analysis at the transcriptome level for L. japonicus that infected with Vibrio anguillarum was performed. In total, 334,388,688 high quality reads were obtained in six libraries (HK-VA, HK-PBS, LI-VA, LI-PBS, SP-VA and SP-PBS) and de novo assembled into 101,860 Unigenes with an average unigene length of 879 bp. Based on sequence similarity 30,142 unigenes (29.59%) were annotated in the public databases. Comparative analysis revealed, 1,202, 3034 and 3519 differentially expressed genes (DEGs) were identified in three comparisons (HK-PBS VS HK-VA, LI-PBS VS LI-VA and SP-PBS VS SP-VA). Enrichment and pathway analysis of the DEGs was also carried out to excavate the candidate genes related to immunity. In conclusion, this study identifies and evaluates dozen of potential immune related pathways and candidate genes, which are indispensable for padding genomic resources of L. japonicus, and would lay the foundation for further studying and illuminating the mechanism of host-pathogen interactions. (C) 2016 Elsevier Ltd. All rights reserved."
1,3,7,7,4,none,small spatial scale (couple of populations),single species in the wild - environment changing,whole genome,Pathogen,Jacob Roved,2016,https://doi.org/10.1007/s00248-015-0721-5,"Grange, ZL; Gartrell, BD; Biggs, PJ; Nelson, NJ; Anderson, M; French, NP",Microbial Genomics of a Host-Associated Commensal Bacterium in Fragmented Populations of Endangered Takahe,MICROBIAL ECOLOGY,71,1020,1029,,10.1007/s00248-015-0721-5,"Isolation of wildlife into fragmented populations as a consequence of anthropogenic-mediated environmental change may alter host-pathogen relationships. Our understanding of some of the epidemiological features of infectious disease in vulnerable populations can be enhanced by the use of commensal bacteria as a proxy for invasive pathogens in natural ecosystems. The distinctive population structure of a well-described meta-population of a New Zealand endangered flightless bird, the takahe (Porphyrio hochstetteri), provided a unique opportunity to investigate the influence of host isolation on enteric microbial diversity. The genomic epidemiology of a prevalent rail-associated endemic commensal bacterium was explored using core genome and ribosomal multilocus sequence typing (rMLST) of 70 Campylobacter sp. nova 1 isolated from one third of the takahe population resident in multiple locations. While there was evidence of recombination between lineages, bacterial divergence appears to have occurred and multivariate analysis of 52 rMLST genes revealed location-associated differentiation of C. sp. nova 1 sequence types. Our results indicate that fragmentation and anthropogenic manipulation of populations can influence host-microbial relationships, with potential implications for niche adaptation and the evolution of micro-organisms in remote environments. This study provides a novel framework in which to explore the complex genomic epidemiology of micro-organisms in wildlife populations."
1,2,7,5,3,none,local (one population),single species in the wild - environment changing,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Pathogen,Jacob Roved,2016,https://doi.org/10.1016/j.sjbs.2015.12.002,"Kumar, KNS; Maruthi, KR; Alfarhan, AH; Rajakrishnan, R; Thomas, J",Molecular fingerprinting of Helicanthus elastica (Desr.) Danser growing on five different hosts by RAPD,SAUDI JOURNAL OF BIOLOGICAL SCIENCES,23,335,340,,10.1016/j.sjbs.2015.12.002,"Mistletoes are hemiparasitic plants growing on aerial parts of other host trees. Many of the mistletoes are reported to be medicinally important. The hemiparasitic nature of these plants makes their chemical composition dependent on the host on which it grows. They are shown to exhibit morphological dissimilarities also when growing on different hosts. Helicanthus elastica (Desr.) Danser (mango mistletoe) is one such less explored medicinal mistletoe found on almost every mango tree in India. Traditionally, the leaves of this plant are used for checking abortion and for removing stones in the kidney and urinary bladder while significant antioxidant and antimicrobial properties are also attributed to this species of mistletoe. The current study was undertaken to evaluate molecular differences in the genomic DNA of the plant while growing on five different host trees using four random markers employing random amplified polymorphic DNA (RAPD) followed by similarity matrix by Jaccard's coefficient and distance matrix by hierarchal clustering analysis. Similarity and distance matrix data employing just 4 random markers, separately and the pooled data as well, revealed significant difference in the genomic DNA of H. elastica growing on five different hosts. Pooled data of similarity from all the 4 primers cumulatively showed similarity between 0.256 and 0.311. Distance matrix ranged from of 0.256 to 0.281 on pooling the data from all the four primers. The result employing a minimum number of primers could conclude that genomic DNA of H. elastica differs depending upon the host on which it grows, hence the host must be considered while studying or utilizing this mistletoe for medicinal purposes. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University."
1,1,9,6,2,none,no spatial aspect,multiple species in the wild - environment changing,exome/transcriptome,Pathogen,Jacob Roved,2016,https://doi.org/10.1186/s13073-016-0293-0,"Grassl, N; Kulak, NA; Pichler, G; Geyer, PE; Jung, J; Schubert, S; Sinitcyn, P; Cox, J; Mann, M",Ultra-deep and quantitative saliva proteome reveals dynamics of the oral microbiome,GENOME MEDICINE,8,,,44,10.1186/s13073-016-0293-0,"Background: The oral cavity is home to one of the most diverse microbial communities of the human body and a major entry portal for pathogens. Its homeostasis is maintained by saliva, which fulfills key functions including lubrication of food, pre-digestion, and bacterial defense. Consequently, disruptions in saliva secretion and changes in the oral microbiome contribute to conditions such as tooth decay and respiratory tract infections. Here we set out to quantitatively map the saliva proteome in great depth with a rapid and in-depth mass spectrometry-based proteomics workflow. Methods: We used recent improvements in mass spectrometry (MS)-based proteomics to develop a rapid workflow for mapping the saliva proteome quantitatively and at great depth. Standard clinical cotton swabs were used to collect saliva form eight healthy individuals at two different time points, allowing us to study interindividual differences and interday changes of the saliva proteome. To accurately identify microbial proteins, we developed a method called ""split by taxonomy id"" that prevents peptides shared by humans and bacteria or between different bacterial phyla to contribute to protein identification. Results: Microgram protein amounts retrieved from cotton swabs resulted in more than 3700 quantified human proteins in 100-min gradients or 5500 proteins after simple fractionation. Remarkably, our measurements also quantified more than 2000 microbial proteins from 50 bacterial genera. Co-analysis of the proteomics results with next-generation sequencing data from the Human Microbiome Project as well as a comparison to MALDI-TOF mass spectrometry on microbial cultures revealed strong agreement. The oral microbiome differs between individuals and changes drastically upon eating and tooth brushing. Conclusion: Rapid shotgun and robust technology can now simultaneously characterize the human and microbiome contributions to the proteome of a body fluid and is therefore a valuable complement to genomic studies. This opens new frontiers for the study of host-pathogen interactions and clinical saliva diagnostics."
2,2,6,6,4,within an individuals lifespan (single generation),local (one population),single species in the wild - environment constant,exome/transcriptome,Host,Jacob Roved,2016,https://doi.org/10.1016/j.gene.2016.01.007,"Li, SS; Zhong, X; Kan, XT; Gu, L; Sun, HX; Zhang, GR; Liu, X","De novo transcriptome analysis of Thitarodes jiachaensis before and after infection by the caterpillar fungus, Ophiocordyceps sinensis",GENE,580,96,103,,10.1016/j.gene.2016.01.007,"Thitarodes jiachaensis is a host species of the pathogenic caterpillar fungus Ophiocordyceps sinensis, which is a fungus with broad medical effects and great economic value. Curated genomic information on Thitarodes is still limited, and the interaction between host Thitarodes larvae and O. sinensis during infection is incompletely understood. In this study, we performed transcriptome sequencing for T. jiachaensis before and after O. sinensis infection using the Illumina sequencing platform, and we identified the transcripts associated with the defense response of T. jiachaensis upon O. sinensis infection. A total of 161,804 transcripts and 94,827 unigenes for T. jiachaensis were obtained from 26.62-Gb clean reads, and 35.03% of all the unigenes were annotated in current databases. The expression of 1581 genes was significantly altered following infection; among them, 928 (58.70%) were up-regulated and 653 (41.30%) were down-regulated. Genes encoding physical barriers such as cuticle proteins and peritrophic matrix proteins, antimicrobial peptides (AMPs), pattern recognition receptors (PRRs), and enzymes in the proteolytic cascade were predicted to be involved in the response of T. jiachaensis to O. sinensis infection. Together, these data provide a valuable genomic resource for further studies of Thitarodes and increase our understanding of the host-pathogen interaction that occurs between Thitarodes and O. sinensis. (C) 2016 Elsevier B.V. All rights reserved."
1,1,6,7,2,none,no spatial aspect,single species in the wild - environment constant,whole genome,Pathogen,Jacob Roved,2016,https://doi.org/10.1186/s40793-016-0149-7,"Almeida, S; Tiwari, S; Mariano, D; Souza, F; Jamal, SB; Coimbra, N; Raittz, RT; Dorella, FA; de Carvalho, AF; Pereira, FL; Soares, SD; Leal, CAG; Barh, D; Ghosh, P; Figueiredo, H; Moura-Costa, LF; Portela, RW; Meyer, R; Silva, A; Azevedo, V",The genome anatomy of Corynebacterium pseudotuberculosis VD57 a highly virulent strain causing Caseous lymphadenitis,STANDARDS IN GENOMIC SCIENCES,11,,,29,10.1186/s40793-016-0149-7,"Corynebacterium pseudotuberculosis strain VD57 (Cp_VD57), a highly virulent, nonmotile, non-sporulating, and a mesophilic bacterium, was isolated from a goat's granulomatous lesion in the municipality of Juazeiro, Bahia State, Brazil. Here, we describe a set of features of the strain, together with the details of its complete genome sequence and annotation. The genome comprises of a 2.5 Mbp long, single circular genome with 2,101 protein-coding genes, 12 rRNA, 49 tRNA and 47 pseudogenes and a G + C content of 52.85 %. Genetic variation was detected in Cp_VD57 using C. pseudotuberculosis strain 1002 as reference, wherein small genomic insertions and deletions were identified. The comparative analysis of the genome sequence provides means to better understand the host pathogen interactions of this strain and can also help us to understand the molecular and genetic basis of virulence of this bacterium."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,both,Jacob Roved,2016,https://doi.org/10.1371/journal.pone.0152908,"Chu, ZJ; Wang, YJ; Ying, SH; Wang, XW; Feng, MG",Genome-Wide Host-Pathogen Interaction Unveiled by Transcriptomic Response of Diamondback Moth to Fungal Infection,PLOS ONE,11,,,e0152908,10.1371/journal.pone.0152908,"Genome-wide insight into insect pest response to the infection of Beauveria bassiana (fungal insect pathogen) is critical for genetic improvement of fungal insecticides but has been poorly explored. We constructed three pairs of transcriptomes of Plutella xylostella larvae at 24, 36 and 48 hours post treatment of infection (hpt(I)) and of control (hpt(C)) for insight into the host-pathogen interaction at genomic level. There were 2143, 3200 and 2967 host genes differentially expressed at 24, 36 and 48 hpt(I)/ hpt(C) respectively. These infection-responsive genes (similar to 15% of the host genome) were enriched in various immune processes, such as complement and coagulation cascades, protein digestion and absorption, and drug metabolism- cytochrome P450. Fungal penetration into cuticle and host defense reaction began at 24 hpt(I), followed by most intensive host immune response at 36 hpt(I) and attenuated immunity at 48 hpt(I). Contrastingly, 44% of fungal genes were differentially expressed in the infection course and enriched in several biological processes, such as antioxidant activity, peroxidase activity and proteolysis. There were 1636 fungal genes co-expressed during 24-48 hpt(I), including 116 encoding putative secretion proteins. Our results provide novel insights into the insect-pathogen interaction and help to probe molecular mechanisms involved in the fungal infection to the global pest."
1,1,2,1,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Host,Jacob Roved,2016,https://doi.org/10.1016/j.fsi.2016.01.043,"Huang, X; Li, W; Jin, M; Ma, FT; Huang, Y; Shi, YR; Zhao, LL; Feng, JL; Ren, Q; Wang, W",Single CRD containing lectin from Macrobrachium rosenbergii (MrLec) participates in innate immunity against pathogen infections,FISH & SHELLFISH IMMUNOLOGY,51,282,290,,10.1016/j.fsi.2016.01.043,"As a type of pattern-recognition proteins, lectins perform important functions in the innate immunity of crustaceans, including prawns. Although several reports showed that C-type lectin domain family (CLEC) importantly functions in host pathogen interactions, limited research has focused on CLEC in Macro brachium rosenbergii. In the present study, a new single CRD containing CLEC (designated as MrLec) was reported in freshwater prawns, M. rosenbergii. The full-length cDNA of MrLec consisted of 1027 bp with an open reading frame of 801 bp, which encoded a peptide of 266 amino acid residues. Genomic sequence for MrLec was also obtained from the M. rosenbergii, which contain 4 exons and 3 introns. MrLec was found to contain a single carbohydrate-recognition domain with an EPN motif. MrLec was ubiquitously distributed in various tissues of a normal prawn, particularly in the hepatopancreas and gills. MrLec expression in the gills was significantly upregulated after a challenge with Vibrio parahaemolyticus and downregulated at 24 h after MrLec RNA interference (MrLec-RNAi). The expression levels of some AMPs, including antilipopolysaccharide factor 1 (Alf1) and lysozyme 2 (Lysol), also markedly decreased after MrLec-RNA1. Recombinant MrLec can agglutinate (Ca2+-dependent) and bind both Gram-negative and Gram-positive bacteria. Results suggested that MrLec participates in the recognition of invading pathogens and functions in the immune response of prawn against pathogen infections. (C) 2016 Elsevier Ltd. All rights reserved."
4,1,6,7,5,many generations,no spatial aspect,single species in the wild - environment constant,whole genome,Pathogen,Jacob Roved,2016,https://doi.org/10.1093/cid/civ1221,"Marzel, A; Desai, PT; Goren, A; Schorr, YI; Nissan, I; Porwollik, S; Valinsky, L; McClelland, M; Rahav, G; Gal-Mor, O",Persistent Infections by Nontyphoidal Salmonella in Humans: Epidemiology and Genetics,CLINICAL INFECTIOUS DISEASES,62,879,886,,10.1093/cid/civ1221,"Background. Although chronic infections by typhoidal Salmonella are well-known, prolonged human infections by nontyphoidal Salmonella (NTS) are poorly characterized. Methods. We retrospectively analyzed 48 345 culture-confirmed NTS infections that occurred in Israel 1995-2012. A case-control study was performed to identify risk factors associated with persistent infections. Whole-genome-sequencing, pulsed-field gel electrophoresis (PFGE), and a mouse infection model were used to study genetic and phenotypic differences between same-patient persistent, recurring isolates. Results. In total, 1047 cases of persistent NTS infections, comprising 2.2% of all reported cases of salmonellosis, were identified. The persistence periods ranged between 30 days to 8.3 years. The majority (93%) of the persistently infected patients were immunocompetent, and 65% were symptomatic with relapsing diarrhea, indicating a distinct clinical manifestation from the asymptomatic carriage of typhoidal Salmonella. Four NTS serovars (Mbandaka, Bredeney, Infantis and Virchow) were found to be significantly more frequently associated with persistence than others. Comparative genomics between early and later isolates obtained from the same patients confirmed clonal infection and showed 0 to 10 SNPs between persistent isolates. A different composition of mobile genetic elements (plasmids and phages) or amino acid substitutions in global regulators was identified in multiple cases. These changes resulted in differences in phenotype and virulence between early and later same-patient isolates. Conclusions. These results illuminate the overlooked clinical manifestation of persistent salmonellosis that can serve as a human reservoir for NTS infections. Additionally, we demonstrate mechanisms of in-host microevolution and exhibit their potential to shape Salmonella pathogenicity, antimicrobial resistance and host-pathogen interactions."
1,1,4,7,2,none,no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Pathogen,Jacob Roved,2016,https://doi.org/10.1007/s00438-015-1135-2,"Martins-Pinheiro, M; Schons-Fonseca, L; da Silva, JB; Domingos, RH; Momo, LHS; Simoes, ACQ; Ho, PL; da Costa, RMA",Genomic survey and expression analysis of DNA repair genes in the genus Leptospira,MOLECULAR GENETICS AND GENOMICS,291,703,722,,10.1007/s00438-015-1135-2,"Leptospirosis is an emerging zoonosis with important economic and public health consequences and is caused by pathogenic leptospires. The genus Leptospira belongs to the order Spirochaetales and comprises saprophytic (L. biflexa), pathogenic (L. interrogans) and host-dependent (L. borgpetersenii) members. Here, we present an in silico search for DNA repair pathways in Leptospira spp. The relevance of such DNA repair pathways was assessed through the identification of mRNA levels of some genes during infection in animal model and after exposition to spleen cells. The search was performed by comparison of available Leptospira spp. genomes in public databases with known DNA repair-related genes. Leptospires exhibit some distinct and unexpected characteristics, for instance the existence of a redundant mechanism for repairing a chemically diverse spectrum of alkylated nucleobases, a new mutS-like gene and a new shorter version of uvrD. Leptospira spp. shares some characteristics from Gram-positive, as the presence of PcrA, two RecQ paralogs and two SSB proteins; the latter is considered a feature shared by naturally competent bacteria. We did not find a significant reduction in the number of DNA repair-related genes in both pathogenic and host-dependent species. Pathogenic leptospires were enriched for genes dedicated to base excision repair and non-homologous end joining. Their evolutionary history reveals a remarkable importance of lateral gene transfer events for the evolution of the genus. Up-regulation of specific DNA repair genes, including components of SOS regulon, during infection in animal model validates the critical role of DNA repair mechanisms for the complex interplay between host/pathogen."
1,1,2,5,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Jacob Roved,2016,https://doi.org/10.1007/s00122-015-2659-x,"Dawson, AM; Ferguson, JN; Gardiner, M; Green, P; Hubbard, A; Moscou, MJ",Isolation and fine mapping of Rps6: an intermediate host resistance gene in barley to wheat stripe rust,THEORETICAL AND APPLIED GENETICS,129,831,843,,10.1007/s00122-015-2659-x,"We uncouple host and nonhost resistance in barley to Puccinia striiformis ff. spp. hordei and tritici . We isolate, fine map, and physically anchor Rps6 to chromosome 7H in barley. A plant may be considered a nonhost of a pathogen if all known genotypes of a plant species are resistant to all known isolates of a pathogen species. However, if a small number of genotypes are susceptible to some known isolates of a pathogen species this plant may be considered an intermediate host. Barley (Hordeum vulgare) is an intermediate host for Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust. We wanted to understand the genetic architecture underlying resistance to Pst and to determine whether any overlap exists with resistance to the host pathogen, Puccinia striiformis f. sp. hordei (Psh). We mapped Pst resistance to chromosome 7H and show that host and intermediate host resistance is genetically uncoupled. Therefore, we designate this resistance locus Rps6. We used phenotypic and genotypic selection on F-2:3 families to isolate Rps6 and fine mapped the locus to a 0.1 cM region. Anchoring of the Rps6 locus to the barley physical map placed the region on a single fingerprinted contig spanning a physical region of 267 kb. Efforts are now underway to sequence the minimal tiling path and to delimit the physical region harboring Rps6. This will facilitate additional marker development and permit identification of candidate genes in the region."
5,1,6,4,6,speciation time (small tree),no spatial aspect,single species in the wild - environment constant,"whole plastid genome (mtDNA, apiDNA)",Pathogen,Jacob Roved,2016,https://doi.org/10.1371/journal.pone.0150718,"Samigullin, TH; Logacheva, MD; Penin, AA; Vallejo-Roman, CM",Complete Plastid Genome of the Recent Holoparasite Lathraea squamaria Reveals Earliest Stages of Plastome Reduction in Orobanchaceae,PLOS ONE,11,,,e0150718,10.1371/journal.pone.0150718,"Plants from the family Orobanchaceae are widely used as a model to study different aspects of parasitic lifestyle including host-parasite interactions and physiological and genomic adaptations. Among the latter, the most prominent are those that occurred due to the loss of photosynthesis; they include the reduction of the photosynthesis-related gene set in both nuclear and plastid genomes. In Orobanchaceae, the transition to non-photosynthetic lifestyle occurred several times independently, but only one lineage has been in the focus of evolutionary studies. These studies included analysis of plastid genomes and transcriptomes and allowed the inference of patterns and mechanisms of genome reduction that are thought to be general for parasitic plants. Here we report the plastid genome of Lathraea squamaria, a holoparasitic plant from Orobanchaceae, clade Rhinantheae. We found that in this plant the degree of plastome reduction is the least among non-photosynthetic plants. Like other parasites, Lathraea possess a plastome with elevated absolute rate of nucleotide substitution. The only gene lost is petL, all other genes typical for the plastid genome are present, but some of them-those encoding photosystem components (22 genes), cytochrome b(6)/f complex proteins (4 genes), plastid-encoded RNA polymerase subunits (2 genes), ribosomal proteins (2 genes), ccsA and cemA-are pseudo-genized. Genes for cytochrome b(6)/f complex and photosystems I and II that do not carry nonsense or frameshift mutations have an increased ratio of non-synonymous to synonymous substitution rates, indicating the relaxation of purifying selection. Our divergence time estimates showed that transition to holoparasitism in Lathraea lineage occurred relatively recently, whereas the holoparasitic lineage Orobancheae is about two times older."
2,1,3,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,Host,Jacob Roved,2016,https://doi.org/10.1111/mec.13566,"Lu, YM; Wohlrab, S; Groth, M; Glockner, G; Guillou, L; John, U",Transcriptomic profiling of Alexandrium fundyense during physical interaction with or exposure to chemical signals from the parasite Amoebophrya,MOLECULAR ECOLOGY,25,1294,1307,,10.1111/mec.13566,"Toxic microalgae have their own pathogens, and understanding the way in which these microalgae respond to antagonistic attacks may provide information about their capacity to persist during harmful algal bloom events. Here, we compared the effects of the physical presence of the parasite Amoebophrya sp. and exposure to waterborne cues from cultures infected with this parasite, on gene expression by the toxic dinoflagellates, Alexandrium fundyense. Compared with control samples, a total of 14882 Alexandrium genes were differentially expressed over the whole-parasite infection cycle at three different time points (0, 6 and 96h). RNA sequencing analyses indicated that exposure to the parasite and parasitic waterborne cues produced significant changes in the expression levels of Alexandrium genes associated with specific metabolic pathways. The observed upregulation of genes associated with glycolysis, the tricarboxylic acid cycle, fatty acid -oxidation, oxidative phosphorylation and photosynthesis suggests that parasite infection increases the energy demand of the host. The observed upregulation of genes correlated with signal transduction indicates that Alexandrium could be sensitized by parasite attacks. This response might prime the defence of the host, as indicated by the increased expression of several genes associated with defence and stress. Our findings provide a molecular overview of the response of a dinoflagellate to parasite infection."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Jacob Roved,2016,https://doi.org/10.1016/flip.2016.01.009,"Hasanuzzaman, AM; Robledo, D; Gomez-Tato, A; Alvarez-Dios, JA; Harrison, PW; Cao, A; Fernandez-Boo, S; Villalba, A; Pardo, BG; Martinez, P",De novo transcriptome assembly of Perkinsus olseni trophozoite stimulated in vitro with Manila clam (Ruditapes philippinarum) plasma,JOURNAL OF INVERTEBRATE PATHOLOGY,135,22,33,,10.1016/flip.2016.01.009,"The protistan parasite Perkinsus olseni is a deadly causative agent of perkinsosis, a molluscan disease affecting Manila clam (Ruditapes philippinarum), having a significant impact on world mollusc production. Deciphering the underlying molecular mechanisms in R. philippinarum-P. olseni interaction is crucial for controlling this parasitosis. The present study investigated the transcriptional expression in the parasite trophozoite using RNA-seq. Control and treatment (in vitro challenged with Manila clam-plasma) P. olseni trophozoite RNA were extracted and sequenced on the Illumina HiSeq 2000 instrument using a 100-bp paired-end sequencing strategy. Paired reads (64.7 million) were de novo assembled using Trinity, and the resultant transcripts were further clustered using CAP3. The re-constructed P. olseni transcriptome contains 47,590 unique transcripts of which 23,505 were annotated to 9764 unique proteins. A large number of genes were associated with Gene Ontology terms such as stress and immune-response, cell homeostasis, antioxidation, cell communication, signal transduction, signalling and proteolysis. Among annotated transcripts, a preliminary gene expression analysis detected 679 up-regulated and 478 down-regulated genes, linked to virulence factors, anti-oxidants, adhesion and immune-response molecules. Genes of several metabolic pathways such as DOXPIMEP, FAS II or folate biosynthesis, which are potential therapeutic targets, were identified. This study is the first description of the P. olseni transcriptome, and provides a substantial genomic resource for studying the molecular mechanisms of the host-parasite interaction in perkinsosis. In this sense, it is also the first evaluation of the parasite gene expression after challenge with clam extracellular products. (C) 2016 Elsevier Inc. All rights reserved."
1,1,2,1,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Jacob Roved,2016,https://doi.org/10.1093/nar/gkv1325,"Angulo, J; Ulryck, N; Deforges, J; Chamond, N; Lopez-Lastra, M; Masquida, B; Sargueil, B",LOOP IIId of the HCV IRES is essential for the structural rearrangement of the 40S-HCV IRES complex,NUCLEIC ACIDS RESEARCH,44,1309,1325,,10.1093/nar/gkv1325,"As obligatory intracellular parasites, viruses rely on cellular machines to complete their life cycle, and most importantly they recruit the host ribosomes to translate their mRNA. The Hepatitis C viral mRNA initiates translation by directly binding the 40S ribosomal subunit in such a way that the initiation codon is correctly positioned in the P site of the ribosome. Such a property is likely to be central for many viruses, therefore the description of host-pathogen interaction at the molecular level is instrumental to provide new therapeutic targets. In this study, we monitored the 40S ribosomal subunit and the viral RNA structural rearrangement induced upon the formation of the binary complex. We further took advantage of an IRES viral mutant mRNA deficient for translation to identify the interactions necessary to promote translation. Using a combination of structure probing in solution and molecular modeling we establish a whole atom model which appears to be very similar to the one obtained recently by cryoEM. Our model brings new information on the complex, and most importantly reveals some structural rearrangement within the ribosome. This study suggests that the formation of a ` kissing complex' between the viral RNA and the 18S ribosomal RNA locks the 40S ribosomal subunit in a conformation proficient for translation."
2,1,2,7,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Jacob Roved,2016,https://doi.org/10.1038/srep20316,"McNulty, SN; Strube, C; Rosa, BA; Martin, JC; Tyagi, R; Choi, YJ; Wang, Q; Pepin, KH; Zhang, X; Ozersky, P; Wilson, RK; Sternberg, PW; Gasser, RB; Mitreva, M","Dictyocaulus viviparus genome, variome and transcriptome elucidate lungworm biology and support future intervention",SCIENTIFIC REPORTS,6,,,20316,10.1038/srep20316,"The bovine lungworm, Dictyocaulus viviparus (order Strongylida), is an important parasite of livestock that causes substantial economic and production losses worldwide. Here we report the draft genome, variome, and developmental transcriptome of D. viviparus. The genome (161 Mb) is smaller than those of related bursate nematodes and encodes fewer proteins (14,171 total). In the first genome-wide assessment of genomic variation in any parasitic nematode, we found a high degree of sequence variability in proteins predicted to be involved host-parasite interactions. Next, we used extensive RNA sequence data to track gene transcription across the life cycle of D. viviparus, and identified genes that might be important in nematode development and parasitism. Finally, we predicted genes that could be vital in host-parasite interactions, genes that could serve as drug targets, and putative RNAi effectors with a view to developing functional genomic tools. This extensive, well-curated dataset should provide a basis for developing new anthelmintics, vaccines, and improved diagnostic tests and serve as a platform for future investigations of drug resistance and epidemiology of the bovine lungworm and related nematodes."
5,1,2,7,6,speciation time (small tree),no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Tim Sackton,2016,https://doi.org/10.1038/NMICROBIOL.2015.19,"Boritsch, EC; Frigui, W; Cascioferro, A; Malaga, W; Etienne, G; Laval, F; Pawlik, A; Le Chevalier, F; Orgeur, M; Ma, L; Bouchier, C; Stinear, TP; Supply, P; Majlessi, L; Daffe, M; Guilhot, C; Brosch, R",pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence,NATURE MICROBIOLOGY,1,,,15019,10.1038/NMICROBIOL.2015.19,"Mycobacterium tuberculosis is a major, globally spread, aerosol-transmitted human pathogen, thought to have evolved by clonal expansion from a Mycobacterium canettii-like progenitor. In contrast, extant M. canettii strains are rare, genetically diverse, and geographically restricted mycobacteria of only marginal epidemiological importance. Here, we show that the contrasting evolutionary success of these two groups is linked to loss of lipooligosaccharide biosynthesis and subsequent morphotype changes. Spontaneous smooth-to-rough M. canettii variants were found to be mutated in the polyketide-synthase-encoding pks5 locus and deficient in lipooligosaccharide synthesis, a phenotype restored by complementation. Importantly, these rough variants showed an altered host-pathogen interaction and increased virulence in cellular-and animal-infection models. In one variant, lipooligosaccharide deficiency occurred via homologous recombination between two pks5 genes and removal of the intervening acyltransferase-encoding gene. The resulting single pks5 configuration is similar to that fixed in M. tuberculosis, which is known to lack lipooligosaccharides. Our results suggest that pks5-recombination-mediated bacterial surface remodelling increased virulence, driving evolution from putative generalist mycobacteria towards professional pathogens of mammalian hosts."
4,2,6,5,6,many generations,local (one population),single species in the wild - environment constant,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Pathogen,Tim Sackton,2016,https://doi.org/10.1371/journal.pcbi.1004475,"Chindelevitch, L; Colijn, C; Moodley, P; Wilson, D; Cohen, T",ClassTR: Classifying Within-Host Heterogeneity Based on Tandem Repeats with Application to Mycobacterium tuberculosis Infections,PLOS COMPUTATIONAL BIOLOGY,12,,,e1004475,10.1371/journal.pcbi.1004475,"Genomic tools have revealed genetically diverse pathogens within some hosts. Within-host pathogen diversity, which we refer to as ""complex infection"", is increasingly recognized as a determinant of treatment outcome for infections like tuberculosis. Complex infection arises through two mechanisms: within-host mutation (which results in clonal heterogeneity) and reinfection (which results in mixed infections). Estimates of the frequency of within-host mutation and reinfection in populations are critical for understanding the natural history of disease. These estimates influence projections of disease trends and effects of interventions. The genotyping technique MLVA (multiple loci variable-number tandem repeats analysis) can identify complex infections, but the current method to distinguish clonal heterogeneity from mixed infections is based on a rather simple rule. Here we describe ClassTR, a method which leverages MLVA information from isolates collected in a population to distinguish mixed infections from clonal heterogeneity. We formulate the resolution of complex infections into their constituent strains as an optimization problem, and show its NP-completeness. We solve it efficiently by using mixed integer linear programming and graph decomposition. Once the complex infections are resolved into their constituent strains, ClassTR probabilistically classifies isolates as clonally heterogeneous or mixed by using a model of tandem repeat evolution. We first compare ClassTR with the standard rule-based classification on 100 simulated datasets. ClassTR outperforms the standard method, improving classification accuracy from 48% to 80%. We then apply ClassTR to a sample of 436 strains collected from tuberculosis patients in a South African community, of which 92 had complex infections. We find that ClassTR assigns an alternate classification to 18 of the 92 complex infections, suggesting important differences in practice. By explicitly modeling tandem repeat evolution, ClassTR helps to improve our understanding of the mechanisms driving within-host diversity of pathogens like Mycobacterium tuberculosis."
3,2,2,5,5,few generations,local (one population),single species laboratory system - no environmental aspect,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Tim Sackton,2016,https://doi.org/10.1007/s10681-015-1528-7,"Singh, PK; Crossa, J; Duveiller, E; Singh, RP; Djurle, A",Association mapping for resistance to tan spot induced by Pyrenophora tritici-repentis race 1 in CIMMYTs historical bread wheat set,EUPHYTICA,207,515,525,,10.1007/s10681-015-1528-7,"Tan spot, a major foliar disease of wheat, is caused by an ascomycete Pyrenophora tritici-repentis (PTR). Association mapping on germplasm collection is a novel approach for the discovery and validation of major genes/QTLs for a trait. Linkage disequilibrium, the genetic basis of association mapping, can be an important tool to identify genomic regions associated with tan spot resistance. Association analysis utilizing the population structure and additive genetic covariance between relatives was conducted for tan spot resistance on a set of historical bread wheat germplasm comprising of 170 lines developed at CIMMYT, Mexico with the genotypic data generated with 1644 molecular markers. Tan spot resistance data was obtained by screening the germplasm with PTR race 1 isolate Ptr-1. Two weeks old seedlings were inoculated and rated 8 days later on a lesion type disease scale. Three experiments were conducted in the greenhouse with each experiment as arranged in completely randomized design with two replicates. Over half of the entries were resistant to tan spot induced by PTR race 1. The genome-wide scan revealed significant marker-phenotype associations on the short arm of chromosomes 1A, 1B, and 6B and long arm of chromosomes 4A, 6A(1), 6A(2), 2B, 3B, 5B, and 7B that play an important role in conferring resistance to tan spot. Although some genomic regions contributing to tan spot resistance have been previously identified; novel regions on long arm of chromosomes 6A(1), 6A(2), and 7B, were identified in this study. Findings of this study reveal that a high proportion of CIMMYT wheat germplasm is resistant to tan spot caused by PTR race 1 and genetic base of CIMMYT germplasm resistance involves race specific and non-race specific resistance genes."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Tim Sackton,2016,https://doi.org/10.1080/07060661.2016.1150884,"Segovia, V; Bruce, M; Rupp, JLS; Huang, L; Bakkeren, G; Trick, HN; Fellers, JP","Two small secreted proteins from Puccinia triticina induce reduction of ss-glucoronidase transient expression in wheat isolines containing Lr9, Lr24 and Lr26",CANADIAN JOURNAL OF PLANT PATHOLOGY,38,91,102,,10.1080/07060661.2016.1150884,"Little is known about the molecular interaction of wheat and leaf rust (Puccinia triticina Eriks). However, genomic tools are now becoming available so that the host-pathogen interactions can be better understood. Significant efforts are being placed on understanding the secretomes of various pathogens as secreted peptides are believed to be the best candidates for avirulence effectors. In this work, a P. triticina haustorial cDNA library was evaluated for the presence of proteins containing secretion signals. Ten predicted proteins were found in the library, of which two were expressed in haustorial fractions. Three of the secreted proteins, Pt3, Pt12 and Pt27, were used in biolistic experiments to determine whether they could induce hypersensitive cell death, which is commonly observed in incompatible rust interactions with wheat leaf rust resistance genes. When Pt3 was co-bombarded with a beta-glucoronidase (GUS)-expressing vector into wheat isolines with resistance genes Lr9 or Lr24, a significant reduction of GUS expression was observed, presumably due to hypersensitive cell death. In other co-bombardment experiments, Pt27 induced a significant reduction in GUS expression in the Lr26 isoline. These results suggest that Pt3 and Pt27 may function in avirulence against wheat leaf rust in resistant genotypes."
4,2,6,7,6,many generations,local (one population),single species in the wild - environment constant,whole genome,Pathogen,Tim Sackton,2016,https://doi.org/10.1155/2016/4512493,"Du, HH; Fang, RD; Pan, TT; Li, T; Li, NZ; He, Q; Wu, R; Peng, YY; Zhou, ZY",Comparative Genomics Analysis of Two Different Virulent Bovine Pasteurella multocida Isolates,INTERNATIONAL JOURNAL OF GENOMICS,NA,,,4512493,10.1155/2016/4512493,"The Pasteurella multocida capsular type A isolates can cause pneumonia and bovine respiratory disease (BRD). In this study, comparative genomics analysis was carried out to identify the virulence genes in two different virulent P. multocida capsular type A isolates (high virulent PmCQ2 and low virulent PmCQ6). The draft genome sequence of PmCQ2 is 2.32 Mbp and contains 2,002 protein-coding genes, 9 insertion sequence (IS) elements, and 1 prophage region. The draft genome sequence of PmCQ6 is 2.29 Mbp and contains 1,970 protein-coding genes, 2 IS elements, and 3 prophage regions. The genome alignment analysis revealed that the genome similarity between PmCQ2 and PmCQ6 is 99% with high colinearity. To identify the candidate genes responsible for virulence, the PmCQ2 and PmCQ6 were compared together with that of the published genomes of high virulent Pm 36950 and PmHN06 and avirulent Pm3480 and Pm70 (capsular type F). Five genes and two insertion sequences are identified in high virulent strains but not in low virulent or avirulent strains. These results indicated that these genes or insertion sequences might be responsible for the virulence of P. multocida, providing prospective candidates for further studies on the pathogenesis and the host-pathogen interactions of P. multocida."
2,3,3,5,5,within an individuals lifespan (single generation),small spatial scale (couple of populations),single species laboratory system - environmental aspect present,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Tim Sackton,2016,https://doi.org/10.1002/ece3.1843,"Manfredini, F; Shoemaker, D; Grozinger, CM",Dynamic changes in host-virus interactions associated with colony founding and social environment in fire ant queens (Solenopsis invicta),ECOLOGY AND EVOLUTION,6,233,244,,10.1002/ece3.1843,"The dynamics of host-parasite interactions can change dramatically over the course of a chronic infection as the internal (physiological) and external (environmental) conditions of the host change. When queens of social insects found a colony, they experience changes in both their physiological state (they develop their ovaries and begin laying eggs) and the social environment (they suddenly stop interacting with the other members of the mother colony), making this an excellent model system for examining how these factors interact with chronic infections. We investigated the dynamics of host-viral interactions in queens of Solenopsis invicta (fire ant) as they transition from mating to colony founding/brood rearing to the emergence of the first workers. We examined these dynamics in naturally infected queens in two different social environments, where queens either founded colonies as individuals or as pairs. We hypothesized that stress associated with colony founding plays an important role in the dynamics of host-parasite interactions. We also hypothesized that different viruses have different modalities of interaction with the host that can be quantified by physiological measures and genomic analysis of gene expression in the host. We found that the two most prevalent viruses, SINV-1 and SINV-2, are associated with different fitness costs that are mirrored by different patterns of gene expression in the host. In fact SINV-2, the virus that imposes the significant reduction of a queen's reproductive output is also associated with larger changes of global gene expression in the host. These results show the complexity of interactions between S. invicta and two viral parasites. Our findings also show that chronic infections by viral parasites in insects are dynamic processes that may pose different challenges in the host, laying the groundwork for interesting ecological and evolutionary considerations."
1,1,6,6,2,none,no spatial aspect,single species in the wild - environment constant,exome/transcriptome,both,Tim Sackton,2016,https://doi.org/10.1155/2016/2741038,"Samant, M; Chadha, N; Tiwari, AK; Hasija, Y",In Silico Designing and Analysis of Inhibitors against Target Protein Identified through Host-Pathogen Protein Interactions in Malaria,INTERNATIONAL JOURNAL OF MEDICINAL CHEMISTRY,NA,,,UNSP 2741038,10.1155/2016/2741038,"Malaria, a life-threatening blood disease, has been a major concern in the field of healthcare. One of the severe forms of malaria is caused by the parasite Plasmodium falciparum which is initiated through protein interactions of pathogen with the host proteins. It is essential to analyse the protein-protein interactions among the host and pathogen for better understanding of the process and characterizing specific molecular mechanisms involved in pathogen persistence and survival. In this study, a complete protein-protein interaction network of human host and Plasmodium falciparum has been generated by integration of the experimental data and computationally predicting interactions using the interolog method. The interacting proteins were filtered according to their biological significance and functional roles. alpha-tubulin was identified as a potential protein target and inhibitors were designed against it by modification of amiprophos methyl. Docking and binding affinity analysis showed two modified inhibitors exhibiting better docking scores of -10.5 kcal/mol and -10.43 kcal/mol and an improved binding affinity of -83.80 kJ/mol and -98.16 kJ/mol with the target. These inhibitors can further be tested and validated in vivo for their properties as an antimalarial drug."
2,1,6,6,3,within an individuals lifespan (single generation),no spatial aspect,single species in the wild - environment constant,exome/transcriptome,Host,Tim Sackton,2016,https://doi.org/10.1016/j.funbio.2015.10.010,"Harris, LJ; Balcerzak, M; Johnston, A; Schneiderman, D; Ouellet, T","Host-preferential Fusarium graminearum gene expression during infection of wheat, barley, and maize",FUNGAL BIOLOGY,120,111,123,,10.1016/j.funbio.2015.10.010,"Fusarium graminearum is a broad host pathogen threatening cereal crops in temperate regions around the world. To better understand how F. graminearum adapts to different hosts, we have performed a comparison of the transcriptome of a single strain of F. graminearum during early infection (up to 4 d post-inoculation) of barley, maize, and wheat using custom oligomer microarrays. Our results showed high similarity between F. graminearum transcriptomes in infected wheat and barley spike tissues. Quantitative RT-PCR was used to validate the gene expression profiles of 24 genes. Host-specific expression of genes was observed in each of the three hosts. This included expression of distinct sets of genes associated with transport and secondary metabolism in each of the three crops, as well as host-specific patterns for particular gene categories such as sugar transporters, integral membrane protein PTH11-like proteins, and chitinases. This study identified 69 F. graminearum genes as preferentially expressed in developing maize kernels relative to wheat and barley spikes. These host-specific differences showcase the genomic flexibility of F. graminearum to adapt to a range of hosts. Crown Copyright (C) 2015 Published by Elsevier Ltd on behalf of The British Mycological Society."
2,1,3,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,both,Tim Sackton,2015,https://doi.org/10.1186/s12864-015-2351-1,"Wallqvist, A; Memisevic, V; Zavaljevski, N; Pieper, R; Rajagopala, SV; Kwon, K; Yu, CG; Hoover, TA; Reifman, J",Using host-pathogen protein interactions to identify and characterize Francisella tularensis virulence factors,BMC GENOMICS,16,,,1106,10.1186/s12864-015-2351-1,"Background: Francisella tularensis is a select bio-threat agent and one of the most virulent intracellular pathogens known, requiring just a few organisms to establish an infection. Although several virulence factors are known, we lack an understanding of virulence factors that act through host-pathogen protein interactions to promote infection. To address these issues in the highly infectious F. tularensis subsp. tularensis Schu S4 strain, we deployed a combined in silico, in vitro, and in vivo analysis to identify virulence factors and their interactions with host proteins to characterize bacterial infection mechanisms. Results: We initially used comparative genomics and literature to identify and select a set of 49 putative and known virulence factors for analysis. Each protein was then subjected to proteome-scale yeast two-hybrid (Y2H) screens with human and murine cDNA libraries to identify potential host-pathogen protein-protein interactions. Based on the bacterial protein interaction profile with both hosts, we selected seven novel putative virulence factors for mutant construction and animal validation experiments. We were able to create five transposon insertion mutants and used them in an intranasal BALB/c mouse challenge model to establish 50 % lethal dose estimates. Three of these, Delta FTT0482c, Delta FTT1538c, and Delta FTT1597, showed attenuation in lethality and can thus be considered novel F. tularensis virulence factors. The analysis of the accompanying Y2H data identified intracellular protein trafficking between the early endosome to the late endosome as an important component in virulence attenuation for these virulence factors. Furthermore, we also used the Y2H data to investigate host protein binding of two known virulence factors, showing that direct protein binding was a component in the modulation of the inflammatory response via activation of mitogen-activated protein kinases and in the oxidative stress response. Conclusions: Direct interactions with specific host proteins and the ability to influence interactions among host proteins are important components for F. tularensis to avoid host-cell defense mechanisms and successfully establish an infection. Although direct host-pathogen protein-protein binding is only one aspect of Francisella virulence, it is a critical component in directly manipulating and interfering with cellular processes in the host cell."
1,2,6,6,3,none,local (one population),single species in the wild - environment constant,exome/transcriptome,Host,Tim Sackton,2015,https://doi.org/10.1186/s12864-015-2277-7,"Visser, EA; Wegrzyn, JL; Steenkmap, ET; Myburg, AA; Naidoo, S",Combined de novo and genome guided assembly and annotation of the Pinus patula juvenile shoot transcriptome,BMC GENOMICS,16,,,1057,10.1186/s12864-015-2277-7,"Background: Pines are the most important tree species to the international forestry industry, covering 42 % of the global industrial forest plantation area. One of the most pressing threats to cultivation of some pine species is the pitch canker fungus, Fusarium circinatum, which can have devastating effects in both the field and nursery. Investigation of the Pinus-F. circinatum host-pathogen interaction is crucial for development of effective disease management strategies. As with many non-model organisms, investigation of host-pathogen interactions in pine species is hampered by limited genomic resources. This was partially alleviated through release of the 22 Gbp Pinus taeda v1.01 genome sequence (http://pinegenome.org/pinerefseq/) in 2014. Despite the fact that the fragmented state of the genome may hamper comprehensive transcriptome analysis, it is possible to leverage the inherent redundancy resulting from deep RNA sequencing with Illumina short reads to assemble transcripts in the absence of a completed reference sequence. These data can then be integrated with available genomic data to produce a comprehensive transcriptome resource. The aim of this study was to provide a foundation for gene expression analysis of disease response mechanisms in Pinus patula through transcriptome assembly. Results: Eighteen de novo and two reference based assemblies were produced for P. patula shoot tissue. For this purpose three transcriptome assemblers, Trinity, Velvet/OASES and SOAPdenovo-Trans, were used to maximise diversity and completeness of assembled transcripts. Redundancy in the assembly was reduced using the EvidentialGene pipeline. The resulting 52 Mb P. patula v1.0 shoot transcriptome consists of 52 112 unigenes, 60 % of which could be functionally annotated. Conclusions: The assembled transcriptome will serve as a major genomic resource for future investigation of P. patula and represents the largest gene catalogue produced to date for this species. Furthermore, this assembly can help detect gene-based genetic markers for P. patula and the comparative assembly workflow could be applied to generate similar resources for other non-model species."
1,1,6,6,2,none,no spatial aspect,single species in the wild - environment constant,exome/transcriptome,Host,Tim Sackton,2015,https://doi.org/10.1186/s12864-015-2124-x,"Lee, AK; Kulcsar, KA; Elliott, O; Khiabanian, H; Nagle, ER; Jones, MEB; Amman, BR; Sanchez-Lockhart, M; Towner, JS; Palacios, G; Rabadan, R",De novo transcriptome reconstruction and annotation of the Egyptian rousette bat,BMC GENOMICS,16,,,1033,10.1186/s12864-015-2124-x,"Background: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. Results: Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. Conclusion: We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission."
1,1,4,2,2,none,no spatial aspect,multiple species laboratory system - no environmental aspect present,full gene/regulator,Host,Tim Sackton,2015,https://doi.org/10.1556/1646.7.2015.4.4,"Khan, N",Comparative and evolutionary insights into CD4 gene across mammalian and avian taxa,INTERVENTIONAL MEDICINE AND APPLIED SCIENCE,7,152,160,,10.1556/1646.7.2015.4.4,"The present day genetic architecture of a species bears much significance to its closely related species which is due to species-specific differences, shaped by different evolutionary forces across time scale. With the availability of whole genome sequence of several closely related species, it is now possible to infer evolutionary patterns of genes and genomes in specific lineages. To this respect, CD4 gene, primarily responsible for defensive mechanism in human, is conserved across a few taxa, and thus, comparative genomic studies could be useful for better understanding of host-pathogen biology. Comparative and evolutionary analyses were performed in eleven taxa (10 mammalian and avian) with different statistical algorithms. Phylogenetic inferences revealed recent divergence of human and chimpanzee, and pig was found to be diverged from rest of the taxa significantly. Additionally, gene length, microsatellites, and secondary structures were observed across taxa. The genetic architecture of CD4 gene and its evolutionary history in different mammalian taxa provide crucial evidence in support of the fact that this gene might have been evolving at a similar rate to other human immune system genes. Future population-based study and structural modeling would unravel the differential ability to interact with HIV virus and influence immune system in humans."
2,1,3,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,Pathogen,Tim Sackton,2015,https://doi.org/10.1371/journal.ppat.1005296,"de Paiva, RMC; Grazielle-Silva, V; Cardoso, MS; Nakagaki, BN; Mendonca-Neto, RP; Canavaci, AMC; Melo, NS; Martinelli, PM; Fernandes, AP; daRocha, WD; Teixeira, SMR",Amastin Knockdown in Leishmania braziliensis Affects Parasite-Macrophage Interaction and Results in Impaired Viability of Intracellular Amastigotes,PLOS PATHOGENS,11,,,e1005296,10.1371/journal.ppat.1005296,"Leishmaniasis, a human parasitic disease with manifestations ranging from cutaneous ulcerations to fatal visceral infection, is caused by several Leishmania species. These protozoan parasites replicate as extracellular, flagellated promastigotes in the gut of a sandfly vector and as amastigotes inside the parasitophorous vacuole of vertebrate host macrophages. Amastins are surface glycoproteins encoded by large gene families present in the genomes of several trypanosomatids and highly expressed in the intracellular amastigote stages of Trypanosoma cruzi and Leishmania spp. Here, we showed that the genome of L. braziliensis contains 52 amastin genes belonging to all four previously described amastin subfamilies and that the expression of members of all subfamilies is upregulated in L. braziliensis amastigotes. Although primary sequence alignments showed no homology to any known protein sequence, homology searches based on secondary structure predictions indicate that amastins are related to claudins, a group of proteins that are components of eukaryotic tight junction complexes. By knocking-down the expression of delta-amastins in L. braziliensis, their essential role during infection became evident. delta-amastin knockdown parasites showed impaired growth after in vitro infection of mouse macrophages and completely failed to produce infection when inoculated in BALB/c mice, an attenuated phenotype that was reverted by the re-expression of an RNAi-resistant amastin gene. Further highlighting their essential role in host-parasite interactions, electron microscopy analyses of macrophages infected with amastin knockdown parasites showed significant alterations in the tight contact that is normally observed between the surface of wild type amastigotes and the membrane of the parasitophorous vacuole."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Host,Allison Shultz,2015,https://doi.org/10.1186/s12864-015-2127-7,"Russo, LM; Abdeltawab, NF; O'Brien, AD; Kotb, M; Melton-Celsa, AR",Mapping of genetic loci that modulate differential colonization by Escherichia coli O157:H7 TUV86-2 in advanced recombinant inbred BXD mice,BMC GENOMICS,16,,,947,10.1186/s12864-015-2127-7,"Background: Shiga toxin (Stx)-producing E. coli (STEC) are responsible for foodborne outbreaks that can result in severe human disease. During an outbreak, differential disease outcomes are observed after infection with the same STEC strain. One question of particular interest is why some infected people resolve infection after hemorrhagic colitis whereas others progress to the hemolytic uremic syndrome (HUS). Host age and infection dose have been implicated; however, these parameters do not appear to fully account for all of the observed variation in disease severity. Therefore, we hypothesized that additional host genetic factors may play a role in progression to HUS. Methods and Results: To mimic the genetic diversity in the human response to infection by STEC, we measured the capacity of an O157:H7 outbreak isolate to colonize mouse strains from the advanced recombinant inbred (ARI) BXD panel. We first infected the BXD parental strains C57BL/6 J (B6) and DBA/2 J (D2) with either 86-24 (Stx2a+) or TUV86-2, an Stx2a-negative isogenic mutant. Colonization levels were determined in an intact commensal flora (ICF) infection model. We found a significant difference in colonization levels between the parental B6 and D2 strains after infection with TUV86-2 but not with 86-24. This observation suggested that a host factor that may be masked by Stx2a affects O157: H7 colonization in some genetic backgrounds. We then determined the TUV86-2 colonization levels of 24 BXD strains in the ICF model. We identified several quantitative trait loci (QTL) associated with variation in colonization by correlation analyses. We found a highly significant QTL on proximal chromosome 9 (12.5-26.7 Mb) that strongly predicts variation in colonization levels and accounts for 15-20 % of variance. Linkage, polymorphism and co-citation analyses of the mapped region revealed 36 candidate genes within the QTL, and we identified five genes that are most likely responsible for the differential colonization. Conclusions: The identification of the QTL on chromosome 9 supports our hypothesis that individual genetic makeup affects the level of colonization after infection with STEC O157: H7."
1,3,6,7,4,none,small spatial scale (couple of populations),single species in the wild - environment constant,whole genome,Pathogen,Allison Shultz,2015,https://doi.org/10.1093/gbe/evv198,"Chiara, M; Fanelli, F; Mule, G; Logrieco, AF; Pesole, G; Leslie, JF; Horner, DS; Toomajian, C",Genome Sequencing of Multiple Isolates Highlights Subtelomeric Genomic Diversity within Fusarium fujikuroi,GENOME BIOLOGY AND EVOLUTION,7,3062,3069,,10.1093/gbe/evv198,"Comparisons of draft genome sequences of three geographically distinct isolates of Fusarium fujikuroi with two recently published genome sequences from the same species suggest diverse profiles of secondary metabolite production within F. fujikuroi. Species- and lineage-specific genes, many of which appear to exhibit expression profiles that are consistent with roles in host-pathogen interactions and adaptation to environmental changes, are concentrated in subtelomeric regions. These genomic compartments also exhibit distinct gene densities and compositional characteristics with respect to other genomic partitions, and likely play a role in the generation of molecular diversity. Our data provide additional evidence that gene duplication, divergence, and differential loss play important roles in F. fujikuroi genome evolution and suggest that hundreds of lineage-specific genes might have been acquired through horizontal gene transfer."
6,1,1,7,7,speciation time (large tree),no spatial aspect,none - theoretical,whole genome,Pathogen,Allison Shultz,2015,https://doi.org/10.1038/ismej.2015.46,"Martijn, J; Schulz, F; Zaremba-Niedzwiedzka, K; Viklund, J; Stepanauskas, R; Andersson, SGE; Horn, M; Guy, L; Ettema, TJG",Single-cell genomics of a rare environmental alphaproteobacterium provides unique insights into Rickettsiaceae evolution,ISME JOURNAL,9,2373,2385,,10.1038/ismej.2015.46,"The bacterial family Rickettsiaceae includes a group of well-known etiological agents of many human and vertebrate diseases, including epidemic typhus-causing pathogen Rickettsia prowazekii. Owing to their medical relevance, rickettsiae have attracted a great deal of attention and their host-pathogen interactions have been thoroughly investigated. All known members display obligate intracellular lifestyles, and the best-studied genera, Rickettsia and Orientia, include species that are hosted by terrestrial arthropods. Their obligate intracellular lifestyle and host adaptation is reflected in the small size of their genomes, a general feature shared with all other families of the Rickettsiales. Yet, despite that the Rickettsiaceae and other Rickettsiales families have been extensively studied for decades, many details of the origin and evolution of their obligate host-association remain elusive. Here we report the discovery and single-cell sequencing of 'Candidatus Arcanobacter lacustris', a rare environmental alphaproteobacterium that was sampled from Damariscotta Lake that represents a deeply rooting sister lineage of the Rickettsiaceae. Intriguingly, phylogenomic and comparative analysis of the partial 'Candidatus Arcanobacter lacustris' genome revealed the presence chemotaxis genes and vertically inherited flagellar genes, a novelty in sequenced Rickettsiaceae, as well as several host-associated features. This finding suggests that the ancestor of the Rickettsiaceae might have had a facultative intracellular lifestyle. Our study underlines the efficacy of single-cell genomics for studying microbial diversity and evolution in general, and for rare microbial cells in particular."
4,1,2,7,5,many generations,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,both,Allison Shultz,2015,https://doi.org/10.1093/molbev/msv160,"Jansen, G; Crummenerl, LL; Gilbert, F; Mohr, T; Pfefferkorn, R; Thanert, R; Rosenstiel, P; Schulenburg, H",Evolutionary Transition from Pathogenicity to Commensalism: Global Regulator Mutations Mediate Fitness Gains through Virulence Attenuation,MOLECULAR BIOLOGY AND EVOLUTION,32,2883,2896,,10.1093/molbev/msv160,"Symbiotic interactions are indispensable for metazoan function, but their origin and evolution remain elusive. We use a controlled evolution experiment to demonstrate the emergence of novel commensal interactions between Pseudomonas aeruginosa, an initially pathogenic bacterium, and a metazoan host, Caenorhabditis elegans. We show that commensalism evolves through loss of virulence, because it provides bacteria with a double fitness advantage: Increased within-host fitness and a larger host population to infect. Commensalism arises irrespective of host immune status, as the adaptive path in immunocompromised C. elegans knockouts does not differ from that in wild type. Dissection of temporal dynamics of genomic adaptation for 125 bacterial populations reveals highly parallel evolution of incipient commensalism across independent biological replicates. Adaptation is mainly achieved through frame shift mutations in the global regulator lasR and nonsynonymous point mutations in the polymerase gene rpoB that arise early in evolution. Genetic knockouts of lasR not only corroborate its role in virulence attenuation but also show that further mutations are necessary for the fully commensal phenotype. The evolutionary transition from pathogenicity to commensalism as we observe here is facilitated by mutations in global regulators such as lasR, because few genetic changes cause pleiotropic effects across the genome with large phenotypic effects. Finally, we found that nucleotide diversity increased more quickly in bacteria adapting to immunocompromised hosts than in those adapting to immunocompetent hosts. Nevertheless, the outcome of evolution was comparable across host types. Commensalism can thus evolve independently of host immune state solely as a side-effect of bacterial adaptation to novel hosts."
1,3,2,7,4,none,small spatial scale (couple of populations),single species laboratory system - no environmental aspect,whole genome,Host,Allison Shultz,2015,https://doi.org/10.1186/s12864-015-2009-z,"Redmond, SN; Eiglmeier, K; Mitri, C; Markianos, K; Guelbeogo, WM; Gneme, A; Isaacs, AT; Coulibaly, B; Brito-Fravallo, E; Maslen, G; Mead, D; Niare, O; Traore, SF; Sagnon, N; Kwiatkowski, D; Riehle, MM; Vernick, KD",Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae,BMC GENOMICS,16,,,779,10.1186/s12864-015-2009-z,"Background: The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods: We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results: In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions: We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour."
4,2,6,7,6,many generations,local (one population),single species in the wild - environment constant,whole genome,Pathogen,Allison Shultz,2015,https://doi.org/10.3389/fmicb.2015.00996,"Atwell, S; Corwin, JA; Soltis, NE; Subedy, A; Denby, KJ; Kliebenstein, DJ",Whole genome resequencing of Botrytis cinerea isolates identifies high levels of standing diversity,FRONTIERS IN MICROBIOLOGY,6,,,996,10.3389/fmicb.2015.00996,"How standing genetic variation within a pathogen contributes to diversity in host/pathogen interactions is poorly understood, partly because most studied pathogens are host-specific, clonally reproducing organisms which complicates genetic analysis. In contrast, Botrytis cinerea is a sexually reproducing, true haploid ascomycete that can infect a wide range of diverse plant hosts. While previous work had shown significant genomic variation between two isolates, we proceeded to assess the level and frequency of standing variation in a population of B. cinerea. To begin measuring standing genetic variation in B. cinerea, we re-sequenced the genomes of 13 different isolates and aligned them to the previously sequenced T4 reference genome. In addition one of these isolates was resequenced from four independently repeated cultures. A high level of genetic diversity was found within the 13 isolates. Within this variation, we could identify clusters of genes with major effect polymorphisms, i.e., polymorphisms that lead to a predicted functional knockout, that surrounded genes involved in controlling vegetative incompatibility. The genotype at these loci was able to partially predict the interaction of these isolates in vegetative fusion assays showing that these loci control vegetative incompatibility. This suggests that the vegetative incompatibility loci within B. cinerea are associated with regions of increased genetic diversity. The genome re-sequencing of four clones from the one isolate (Grape) that had been independently propagated over 10 years showed no detectable spontaneous mutation. This suggests that B. cinerea does not display an elevated spontaneous mutation rate. Future work will allow us to test if, and how, this diversity may be contributing to the pathogen's broad host range."
5,1,8,7,6,speciation time (small tree),no spatial aspect,multiple species in the wild - environment constant,whole genome,Pathogen,Allison Shultz,2015,https://doi.org/10.1186/s12864-015-1889-2,"Timms, VJ; Hassan, KA; Mitchell, HM; Neilan, BA",Comparative genomics between human and animal associated subspecies of the Mycobacterium avium complex: a basis for pathogenicity,BMC GENOMICS,16,,,695,10.1186/s12864-015-1889-2,"Background: A human isolate of Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis 43525) was sequenced and compared genomically to other mycobacterial pathogens. M. paratuberculosis 43525 was recently isolated from a patient with ulcerative colitis and belongs to the M. avium complex, a group known to infect both humans and animals. While M. paratuberculosis is a known pathogen of livestock, there are only 20 human isolates from the last 20 years, therefore we took the opportunity to perform a whole genome comparison between human and animal mycobacterial pathogens. We also compared virulence determinants such as the mycobactin cluster, PE/PPE genes and mammalian cell entry (mce) operons between MAC subspecies that infect animals and those that infect humans. M. tuberculosis was also included in these analyses given its predominant role as a human pathogen. Results: This genome comparison showed the PE/PPE profile of M. paratuberculosis 43525 to be largely the same as other M. paratuberculosis isolates, except that it had one PPE and one PE_PGRS protein that are only present in human MAC strains and M. tuberculosis. PE/PPE proteins that were unique to M. paratuberculosis 43525, M. avium subsp. hominissuis and a caprine M. paratuberculosis isolate, were also identified. In addition, the mycobactin cluster differed between human and animal isolates and a unique mce operon flanked by two mycobactin genes, mbtA and mbtJ, was identified in all available M. paratuberculosis genomes. Conclusions: Despite the whole genome comparison placing M. paratuberculosis 43525 as closely related to bovine M. paratuberculosis, key virulence factors were similar to human mycobacterial pathogens. This study highlights key factors of mycobacterial pathogenesis in humans and forms the basis for future functional studies."
6,1,8,3,7,speciation time (large tree),no spatial aspect,multiple species in the wild - environment constant,gene family/microsatellites,Pathogen,Allison Shultz,2015,https://doi.org/10.1038/srep13032,"Zhang, ZN; Wu, QY; Zhang, GZ; Zhu, YY; Murphy, RW; Liu, Z; Zou, CG",Systematic analyses reveal uniqueness and origin of the CFEM domain in fungi,SCIENTIFIC REPORTS,5,,,13032,10.1038/srep13032,"CFEM domain commonly occurs in fungal extracellular membrane proteins. To provide insights for understanding putative functions of CFEM, we investigate the evolutionary dynamics of CFEM domains by systematic comparative genomic analyses among diverse animals, plants, and more than 100 fungal species, which are representative across the entire group of fungi. We here show that CFEM domain is unique to fungi. Experiments using tissue culture demonstrate that the CFEM-containing ESTs in some plants originate from endophytic fungi. We also find that CFEM domain does not occur in all fungi. Its single origin dates to the most recent common ancestors of Ascomycota and Basidiomycota, instead of multiple origins. Although the length and architecture of CFEM domains are relatively conserved, the domain-number varies significantly among different fungal species. In general, pathogenic fungi have a larger number of domains compared to other species. Domain-expansion across fungal genomes appears to be driven by domain duplication and gene duplication via recombination. These findings generate a clear evolutionary trajectory of CFEM domains and provide novel insights into the functional exchange of CFEM-containing proteins from cell-surface components to mediators in host-pathogen interactions."
1,2,6,2,3,none,local (one population),single species in the wild - environment constant,full gene/regulator,Pathogen,Allison Shultz,2015,https://doi.org/10.1371/journal.pone.0134897,"Origgi, FC; Tecilla, M; Pilo, P; Aloisio, F; Otten, P; Aguilar-Bultet, L; Sattler, U; Roccabianca, P; Romero, CH; Bloom, DC; Jacobson, ER",A Genomic Approach to Unravel Host-Pathogen Interaction in Chelonians: The Example of Testudinid Herpesvirus 3,PLOS ONE,10,,,e0134897,10.1371/journal.pone.0134897,"We report the first de novo sequence assembly and analysis of the genome of Testudinid herpesvirus 3 (TeHV3), one of the most pathogenic chelonian herpesviruses. The genome of TeHV3 is at least 150,080 nucleotides long, is arranged in a type D configuration and comprises at least 102 open reading frames extensively co-linear with those of Human herpesvirus 1. Consistently, the phylogenetic analysis positions TeHV3 among the Alphaherpesvirinae, closely associated with Chelonid herpesvirus 5, a Scutavirus. To date, there has been limited genetic characterization of TeHVs and a resolution beyond the genotype was not feasible because of the lack of informative DNA sequences. To exemplify the potential benefits of the novel genomic information provided by this first whole genome analysis, we selected the glycoprotein B (gB) gene, for detailed comparison among different TeHV3 isolates. The rationale for selecting gB is that it encodes for a well-conserved protein among herpesviruses but is coupled with a relevant antigenicity and is consequently prone to accumulate single nucleotide polymorphisms. These features were considered critical for an ideal phylogenetic marker to investigate the potential existence of distinct TeHV3 genogroups and their associated pathology. Fifteen captive tortoises presumptively diagnosed to be infected with TeHVs or carrying compatible lesions on the basis of either the presence of intranuclear inclusions (presumptively infected) and/or diphtheronecrotic stomatitis-glossitis or pneumonia (compatible lesions) were selected for the study. Viral isolation, TeHV identification, phylogenetic analysis and pathological characterization of the associated lesions, were performed. Our results revealed 1) the existence of at least two distinct TeHV3 genogroups apparently associated with different pathologies in tortoises and 2) the first evidence for a putative homologous recombination event having occurred in a chelonian herpesvirus. This novel information is not only fundamental for the genetic characterization of this virus but is also critical to lay the groundwork for an improved understanding of host-pathogen interactions in chelonians and contribute to tortoise conservation."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Host,Allison Shultz,2015,https://doi.org/10.1002/eji.201545547,"Smith, PM; Sproule, TJ; Philip, VM; Roopenian, DC; Stadecker, MJ",Minor genomic differences between related B6 and B10 mice affect severity of schistosome infection by governing the mode of dendritic cell activation,EUROPEAN JOURNAL OF IMMUNOLOGY,45,2312,2323,,10.1002/eji.201545547,"Infection with the helminth Schistosoma mansoni results in hepatointestinal granulomatous inflammation mediated by CD4 T cells directed against parasite eggs. The severity of disease varies greatly in humans and mice; however, the genetic basis of such a heterogenous immune response remains poorly understood. Here we show that, despite their close genetic relationship, C57BL/10SnJ (B10) mice developed significantly more pronounced immunopathology and higher T helper 17 cell responses than C57BL/6J (B6) mice. Similarly, live egg-stimulated B10-derived dendritic cells (DCs) produced significantly more IL-1 beta and IL-23, resulting in higher IL-17 production by CD4 T cells. Gene expression analysis disclosed a heightened proinflammatory cytokine profile together with a strikingly lower expression of Ym1 in B10 versus B6 mice, consistent with failure of B10 DCs to attain alternative activation. To genetically dissect the differential response, we developed and analyzed congenic mouse strains that capture major regions of allelic variation, and found that the level of inflammation was controlled by a relatively small number of genes in a locus mapping to chromosome 4 117-143 MB. Our study has thus identified novel genomic regions that regulate the severity of the schistosome infection by way of controlling the mode of DC activation and consequent CD4 T-cell subset development."
1,3,6,5,4,none,small spatial scale (couple of populations),single species in the wild - environment constant,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Allison Shultz,2015,https://doi.org/10.1111/mec.13313,"Wenzel, MA; James, MC; Douglas, A; Piertney, SB",Genome-wide association and genome partitioning reveal novel genomic regions underlying variation in gastrointestinal nematode burden in a wild bird,MOLECULAR ECOLOGY,24,4175,4192,,10.1111/mec.13313,"Identifying the genetic architecture underlying complex phenotypes is a notoriously difficult problem that often impedes progress in understanding adaptive eco-evolutionary processes in natural populations. Host-parasite interactions are fundamentally important drivers of evolutionary processes, but a lack of understanding of the genes involved in the host's response to chronic parasite insult makes it particularly difficult to understand the mechanisms of host life history trade-offs and the adaptive dynamics involved. Here, we examine the genetic basis of gastrointestinal nematode (Trichostrongylus tenuis) burden in 695 red grouse (Lagopus lagopus scotica) individuals genotyped at 384 genome-wide SNPs. We first use genome-wide association to identify individual SNPs associated with nematode burden. We then partition genome-wide heritability to identify chromosomes with greater heritability than expected from gene content, due to harbouring a multitude of additive SNPs with individually undetectable effects. We identified five SNPs on five chromosomes that accounted for differences of up to 556 worms per bird, but together explained at best 4.9% of the phenotypic variance. These SNPs were closely linked to genes representing a range of physiological processes including the immune system, protein degradation and energy metabolism. Genome partitioning indicated genome-wide heritability of up to 29% and three chromosomes with excess heritability of up to 4.3% (total 8.9%). These results implicate SNPs and novel genomic regions underlying nematode burden in this system and suggest that this phenotype is somewhere between being based on few large-effect genes (oligogenic) and based on a large number of genes with small individual but large combined effects (polygenic)."
1,1,1,5,2,none,no spatial aspect,none - theoretical,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Pathogen,Allison Shultz,2015,https://doi.org/10.1111/mpp.12214,"Leboldus, JM; Kinzer, K; Richards, J; Ya, Z; Yan, CH; Friesen, TL; Brueggeman, R",Genotype-by-sequencing of the plant-pathogenic fungi Pyrenophora teres and Sphaerulina musiva utilizing Ion Torrent sequence technology,MOLECULAR PLANT PATHOLOGY,16,623,632,,10.1111/mpp.12214,"Genetic and genomics tools to characterize host-pathogen interactions are disproportionately directed to the host because of the focus on resistance. However, understanding the genetics of pathogen virulence is equally important and has been limited by the high cost of denovo genotyping of species with limited marker data. Non-resource-prohibitive methods that overcome the limitation of genotyping are now available through genotype-by-sequencing (GBS). The use of a two-enzyme restriction-associated DNA (RAD)-GBS method adapted for Ion Torrent sequencing technology provided robust and reproducible high-density genotyping of several fungal species. A total of 5783 and 2373 unique loci, sequence tags', containing 16441 and 9992 single nucleotide polymorphisms (SNPs) were identified and characterized from natural populations of Pyrenophora teres f. maculata and Sphaerulina musiva, respectively. The data generated from the P.teres f. maculata natural population were used in association mapping analysis to map the mating-type gene to high resolution. To further validate the methodology, a biparental population of P.teres f. teres, previously used to develop a genetic map utilizing simple sequence repeat (SSR) and amplified fragment length polymorphism (AFLP) markers, was re-analysed using the SNP markers generated from this protocol. A robust genetic map containing 1393 SNPs on 997 sequence tags spread across 15 linkage groups with anchored reference markers was generated from the P.teres f. teres biparental population. The robust high-density markers generated using this protocol will allow positional cloning in biparental fungal populations, association mapping of natural fungal populations and population genetics studies."
3,1,2,2,4,few generations,no spatial aspect,single species laboratory system - no environmental aspect,full gene/regulator,Pathogen,Allison Shultz,2015,https://doi.org/10.1016/j.gene.2015.04.026,"Parvez, MK","The hepatitis E virus ORF1 'X-domain' residues form a putative macrodomain protein/Appr-1 ''-pase catalytic-site, critical for viral RNA replication",GENE,566,47,53,,10.1016/j.gene.2015.04.026,"The hepatitis E virus (HEV) ORF1 gene encodes the non-structural polyprotein wherein the 'X-domain' still remains poorly defined. Cellular X-domain associated macrodomain protein/ADP-ribose-1 ''-monophosphatase (Appr-1 ''-pase) activities are also reported in coronaviruses (Coy), including identification of its homologs in alpha and rubella viruses. The present study investigated the role(s) of X-domain residues in HEV replication cycle. In silico analysis showed a high degree of evolutionary conservation of X-domain (a.a. 785-942) a.a, positions wherein the N-terminus residues 'Asn806, Asn809, His812, G1y815, G1y816, and G1y817' formed a potential catalytic-site homolog of CoVAppr-1 ''-pase. To experimentally test this prediction, X-domain 'active-site' residues were subjected to mutational analysis using the HEV-SAR55 replicon (pSK-GFP). FACS analysis of mutant RNA transfected S10-3 cells showed that G1y816Ala and G1y817Ala constructs completely abrogated HEV replication, similar to their Gly816Val and Gly817Val counterparts. However, 'Gly815Ala' mutant replicated very poorly in contrast to Gly815Val' that completely abolished GFP synthesis. Furthermore, while 'Asn806Ala' mutant retained RNA replication, the 'Asn809Ala' and His812Leu mutants showed non-viability. Notably, in a sequential-nucleotide mutation analysis, the dispensability of X-domain in HEV replication at transcriptional level has already been demonstrated (Parvez, 2013b). Taken together, the present data strongly argue for an essential role of X-domain residues (Asn809, His812, G1y816 and G1y817) at post-translational level, indicating its involvement in viral replication. In conclusion, the speculated regulatory role of ORF1 X-domain in HEV replication cycle critically depends on the 'Am, Asn, His, Gly, Gly, Gly' segment/secondary structure. Nevertheless, further biochemical or biophysical characterizations of HEV X-domain associated Appr-1 ''-pase activity would only confirm its biological significance in virus or host-pathogenesis. (C) 2015 Elsevier B.V. All rights reserved."
1,1,4,6,2,none,no spatial aspect,multiple species laboratory system - no environmental aspect present,exome/transcriptome,Host,Allison Shultz,2015,https://doi.org/10.1371/journal.pone.0130500,"Price, SJ; Garner, TWJ; Balloux, F; Ruis, C; Paszkiewicz, KH; Moore, K; Griffiths, AGF",A de novo Assembly of the Common Frog (Rana temporaria) Transcriptome and Comparison of Transcription Following Exposure to Ranavirus and Batrachochytrium dendrobatidis,PLOS ONE,10,,,e0130500,10.1371/journal.pone.0130500,"Amphibians are experiencing global declines and extinctions, with infectious diseases representing a major factor. In this study we examined the transcriptional response of metamorphic hosts (common frog, Rana temporaria) to the two most important amphibian pathogens: Batrachochytrium dendrobatidis (Bd) and Ranavirus. We found strong up-regulation of a gene involved in the adaptive immune response (AP4S1) at four days post-exposure to both pathogens. We detected a significant transcriptional response to Bd, covering the immune response (innate and adaptive immunity, complement activation, and general inflammatory responses), but relatively little transcriptional response to Ranavirus. This may reflect the higher mortality rates found in wild common frogs infected with Ranavirusas opposed to Bd. These data provide a valuable genomic resource for the amphibians, contribute insight into gene expression changes after pathogen exposure, and suggest potential candidate genes for future host-pathogen research."
2,2,6,6,4,within an individuals lifespan (single generation),local (one population),single species in the wild - environment constant,exome/transcriptome,Host,Vignesh Venkatakrishnan,2015,https://doi.org/10.1186/s12864-015-1667-1,"Verbruggen, B; Bickley, LK; Santos, EM; Tyler, CR; Stentiford, GD; Bateman, KS; van Aerle, R",De novo assembly of the Carcinus maenas transcriptome and characterization of innate immune system pathways,BMC GENOMICS,16,,,458,10.1186/s12864-015-1667-1,"Background: The European shore crab, Carcinus maenas, is used widely in biomonitoring, ecotoxicology and for studies into host-pathogen interactions. It is also an important invasive species in numerous global locations. However, the genomic resources for this organism are still sparse, limiting research progress in these fields. To address this resource shortfall we produced a C. maenas transcriptome, enabled by the progress in next-generation sequencing technologies, and applied this to assemble information on the innate immune system in this species. Results: We isolated and pooled RNA for twelve different tissues and organs from C. maenas individuals and sequenced the RNA using next generation sequencing on an Illumina HiSeq 2500 platform. After de novo assembly a transcriptome was generated encompassing 212,427 transcripts (153,699 loci). The transcripts were filtered, annotated and characterised using a variety of tools (including BLAST, MEGAN and RSEM) and databases (including NCBI, Gene Ontology and KEGG). There were differential patterns of expression for between 1,223 and 2,741 transcripts across tissues and organs with over-represented Gene Ontology terms relating to their specific function. Based on sequence homology to immune system components in other organisms, we show both the presence of transcripts for a series of known pathogen recognition receptors and response proteins that form part of the innate immune system, and transcripts representing the RNAi, Toll-like receptor signalling, IMD and JAK/STAT pathways. Conclusions: We have produced an assembled transcriptome for C. maenas that provides a significant molecular resource for wide ranging studies in this species. Analysis of the transcriptome has revealed the presence of a series of known targets and functional pathways that form part of their innate immune system and illustrate tissue specific differences in their expression patterns."
1,1,4,7,2,none,no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Pathogen,Vignesh Venkatakrishnan,2015,https://doi.org/10.1093/gbe/evv092,"Sperschneider, J; Gardiner, DM; Thatcher, LF; Lyons, R; Singh, KB; Manners, JM; Taylor, JM",Genome-Wide Analysis in Three Fusarium Pathogens Identifies Rapidly Evolving Chromosomes and Genes Associated with Pathogenicity,GENOME BIOLOGY AND EVOLUTION,7,1613,1627,,10.1093/gbe/evv092,"Pathogens and hosts are in an ongoing arms race and genes involved in host-pathogen interactions are likely to undergo diversifying selection. Fusarium plant pathogens have evolved diverse infection strategies, but how they interact with their hosts in the biotrophic infection stage remains puzzling. To address this, we analyzed the genomes of three Fusarium plant pathogens for genes that are under diversifying selection. We found a two-speed genome structure both on the chromosome and gene group level. Diversifying selection acts strongly on the dispensable chromosomes in Fusarium oxysporum f. sp. lycopersici and on distinct core chromosome regions in Fusarium graminearum, all of which have associations with virulence. Members of two gene groups evolve rapidly, namely those that encode proteins with an N-terminal [SG]-P-C-[KR]-P sequence motif and proteins that are conserved predominantly in pathogens. Specifically, 29 F. graminearum genes are rapidly evolving, in planta induced and encode secreted proteins, strongly pointing toward effector function. In summary, diversifying selection in Fusarium is strongly reflected as genomic footprints and can be used to predict a small gene set likely to be involved in host-pathogen interactions for experimental verification."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Vignesh Venkatakrishnan,2015,https://doi.org/10.1093/gbe/evv101,"Li, YY; Liu, Y; Chew, SC; Tay, M; Salido, MMS; Teo, J; Lauro, FM; Givskov, M; Yang, L",Complete Genome Sequence and Transcriptomic Analysis of the Novel Pathogen Elizabethkingia anophelis in Response to Oxidative Stress,GENOME BIOLOGY AND EVOLUTION,7,1676,1685,,10.1093/gbe/evv101,"Elizabethkingia anophelis is an emerging pathogen that can cause life-threatening infections in neonates, severely immunocompromised and postoperative patients. The lack of genomic information on E. anophelis hinders our understanding of its mechanisms of pathogenesis. Here, we report the first complete genome sequence of E. anophelis NUHP1 and assess its response to oxidative stress. Elizabethkingia anophelis NUHP1 has a circular genome of 4,369,828 base pairs and 4,141 predicted coding sequences. Sequence analysis indicates that E. anophelis has well-developed systems for scavenging iron and stress response. Many putative virulence factors and antibiotic resistance genes were identified, underscoring potential host-pathogen interactions and antibiotic resistance. RNA-sequencing-based transcriptome profiling indicates that expressions of genes involved in synthesis of an yersiniabactin-like iron siderophore and heme utilization are highly induced as a protective mechanism toward oxidative stress caused by hydrogen peroxide treatment. Chromeazurol sulfonate assay verified that siderophore production of E. anophelis is increased in the presence of oxidative stress. We further showed that hemoglobin facilitates the growth, hydrogen peroxide tolerance, cell attachment, and biofilm formation of E. anophelis NUHP1. Our study suggests that siderophore production and heme uptake pathways might play essential roles in stress response and virulence of the emerging pathogen E. anophelis."
1,1,2,1,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Vignesh Venkatakrishnan,2015,https://doi.org/,"Wubben, MJ; Gavilano, L; Baum, TJ; Davis, EL",Sequence and Spatiotemporal Expression Analysis of CLE-Motif Containing Genes from the Reniform Nematode (Rotylenchulus reniformis Linford & Oliveira),JOURNAL OF NEMATOLOGY,47,159,165,,,"The reniform nematode, Rotylenchulus reniformis, is a sedentary semi-endoparasitic species with a host range that encompasses more than 77 plant families. Nematode effector proteins containing plant-ligand motifs similar to CLAVATA3/ESR (CLE) peptides have been identified in the Heterodera, Globodera, and Meloidogyne genera of sedentary endoparasites. Here, we describe the isolation, sequence analysis, and spatiotemporal expression of three R. reniformis genes encoding putative CLE motifs named Rr-cle-1, Rr-cle-2, and Rr-cle-3. The Rr-cle cDNAs showed >98% identity with each other and the predicted peptides were identical with the exception of a short stretch of residues at the carboxy(C)-terminus of the variable domain (VD). Each RrCLE peptide possessed an amino-terminal signal peptide for secretion and a single C-terminal CLE motif that was most similar to Heterodera CLE motifs. Aligning the Rr-cle cDNAs with their corresponding genomic sequences showed three exons with an intron separating the signal peptide from the VD and a second intron separating the VD from the CLE motif. An alignment of the RrCLE1 peptide with Heterodera glycines and Heterodera schachtii CLE proteins revealed a high level of homology within the VD region associated with regulating in planta trafficking of the processed CLE peptide. Quantitative RT-PCR (qRT-PCR) showed similar expression profiles for each Rr-cle transcript across the R. reniformis life-cycle with the greatest transcript abundance being in sedentary parasitic female nematodes. In situ hybridization showed specific Rr-cle expression within the dorsal esophageal gland cell of sedentary parasitic females."
2,1,8,3,3,within an individuals lifespan (single generation),no spatial aspect,multiple species in the wild - environment constant,gene family/microsatellites,Pathogen,Vignesh Venkatakrishnan,2015,https://doi.org/10.1016/j.meegid.2015.03.014,"Cwiklinski, K; Allen, K; LaCourse, J; Williams, DJ; Paterson, S; Hodgkinson, JE","Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach",INFECTION GENETICS AND EVOLUTION,32,298,304,,10.1016/j.meegid.2015.03.014,"The liver fluke, Fasciola hepatica is an economically important pathogen of sheep and cattle and has been described by the WHO as a re-emerging zoonosis. Control is heavily reliant on the use of drugs, particularly triclabendazole and as a result resistance has now emerged. The population structure of F. hepatica is not well known, yet it can impact on host-parasite interactions and parasite control with drugs, particularly regarding the spread of triclabendazole resistance. We have identified 2448 potential microsatellites from 83 Mb of F. hepatica genome sequence using msatfinder. Thirty-five loci were developed and optimised for microsatellite PCR, resulting in a panel of 15 polymorphic loci, with a range of three to 15 alleles. This panel was validated on genomic DNA from 46 adult F. hepatica; 38 liver flukes sourced from a Northwest abattoir, UK and 8 liver flukes from an established isolate (Shrewsbury; Ridgeway Research). Evidence for null alleles was found at four lad (Fh_1, Fh_8, Fh_13 and Fh_14), which showed markedly higher levels of homozygosity than the remaining 11 loci. Of the 38 liver flukes isolated from cattle livers (n = 10) at the abattoir, 37 genotypes were identified. Using a multiplex approach all 15 loci could be amplified from several life cycle stages that typically yield low amounts of DNA, including metacercariae, the infective life cycle stage present on pasture, highlighting the utility of this multiplex microsatellite panel. This study reports the largest panel of microsatellite markers available to date for population studies of F. hepatica and the first multiplex panel of microsatellite markers that can be used for several life cycle stages. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)."
3,1,1,3,4,few generations,no spatial aspect,none - theoretical,gene family/microsatellites,both,Vignesh Venkatakrishnan,2015,https://doi.org/10.1016/j.meegid.2015.03.031,"Mukherjee, S; Panda, A; Ghosh, TC",Elucidating evolutionary features and functional implications of orphan genes in Leishmania major,INFECTION GENETICS AND EVOLUTION,32,330,337,,10.1016/j.meegid.2015.03.031,"Orphan genes are protein coding genes that lack recognizable homologs in other organisms. These genes were reported to comprise a considerable fraction of coding regions in all sequenced genomes and thought to be allied with organism's lineage-specific traits. However, their evolutionary persistence and functional significance still remain elusive. Due to lack of homologs with the host genome and for their probable lineage-specific functional roles, orphan gene product of pathogenic protozoan might be considered as the possible therapeutic targets. Leishmania major is an important parasitic protozoan of the genus Leishmania that is associated with the disease cutaneous leishmaniasis. Therefore, evolutionary and functional characterization of orphan genes in this organism may help in understanding the factors prevailing pathogen evolution and parasitic adaptation. In this study, we systematically identified orphan genes of L. major and employed several in silico analyses for understanding their evolutionary and functional attributes. To trace the signatures of molecular evolution, we compared their evolutionary rate with non-orphan genes. In agreement with prior observations, here we noticed that orphan genes evolve at a higher rate as compared to non-orphan genes. Lower sequence conservation of orphan genes was previously attributed solely due to their younger gene age. However, here we observed that together with gene age, a number of genomic (like expression level, GC content, variation in codon usage) and proteomic factors (like protein length, intrinsic disorder content, hydropathicity) could independently modulate their evolutionary rate. We considered the interplay of all these factors and analyzed their relative contribution on protein evolutionary rate by regression analysis. On the functional level, we observed that orphan genes are associated with regulatory, growth factor and transport related processes. Moreover, these genes were found to be enriched with various types of interaction and trafficking motifs, implying their possible involvement in host-parasite interactions. Thus, our comprehensive analysis of L. major orphan genes provided evidence for their extensive roles in host-pathogen interactions and virulence. (C) 2015 Elsevier B.V. All rights reserved."
1,1,2,1,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Vignesh Venkatakrishnan,2015,https://doi.org/10.1016/j.exppara.2015.03.009,"Weiss, PHE; Batista, F; Wagner, G; Magalhaes, MDB; Miletti, LC",Kinetic and biochemical characterization of Trypanosoma evansi nucleoside triphosphate diphosphohydrolase,EXPERIMENTAL PARASITOLOGY,153,98,104,,10.1016/j.exppara.2015.03.009,"Nucleoside triphosphate diphospho-hydrolases (NTPDases) catalyze the hydrolysis of several nucleosides tri and diphosphate playing major roles in eukaryotes including purinergic signaling, inflammation, hemostasis, purine salvage and host-pathogen interactions. These enzymes have been recently described in parasites where several evidences indicated their involvement in virulence and infection. Here, we have investigated the presence of NTPDase in the genome of Tiypanosoma evansi. Based on the genomic sequence from Trypanosoma brucei, we have amplified an 1812 gene fragment corresponding to the T. evansi NTPDase gene. The protein was expressed in the soluble form and purified to homogeneity and enzymatic assays were performed confirming the enzyme identity. Kinetic parameters and substrate specificity were determined. The dependence of cations on enzymatic activity was investigated indicating the enzyme is stimulated by divalent cations and carbohydrates but inhibited by sodium. Bioinformatic analysis indicates the enzyme is a membrane bound protein facing the extracellular side of the cell with 98% identity to the T. brucei homologous NTPDase gene. (C) 2015 Elsevier Inc. All rights reserved."
1,1,1,7,2,none,no spatial aspect,none - theoretical,whole genome,Pathogen,Vignesh Venkatakrishnan,2015,https://doi.org/10.1038/srep09683,"Gomez, S; Adalid-Peralta, L; Palafox-Fonseca, H; Cantu-Robles, VA; Soberon, X; Sciutto, E; Fragoso, G; Bobes, RJ; Laclette, JP; Yauner, LD; Ochoa-Leyva, A",Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR),SCIENTIFIC REPORTS,5,,,9683,10.1038/srep09683,"Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in Taenia solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of Taenia solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of Taenia solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for Taenia solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of Taenia solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest."
1,1,1,1,2,none,no spatial aspect,none - theoretical,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Vignesh Venkatakrishnan,2015,https://doi.org/10.1016/j.molbiopara.2015.05.008,"Wijayawardena, BK; Minchella, DJ; DeWoody, JA",Horizontal gene transfer in schistosomes: A critical assessment,MOLECULAR AND BIOCHEMICAL PARASITOLOGY,201,57,65,,10.1016/j.molbiopara.2015.05.008,"Horizontal gene transfer (HGT), the movement of genetic material between distinct evolutionary lineages, has long been known as a principal force of diversification and adaptation of prokaryotes. More recently, genomic and transcriptomic datasets have suggested gene transfers among various eukaryotic taxa (e.g., Porifera, Cnidaria, Nematoda, Arthropoda, Rotifera, Craniata, and Plantae). Although the exact mechanism of eukaryotic HGT is often unknown, host-parasite interactions may provide ample opportunities for HGT. Schistosomes are trematode blood parasites with complex life cycles that have been repeatedly implicated in HGT. We employed molecular, bioinformatic and phylogenetic approaches to critically analyze 13 published reports of direct HGTs between schistosomes and their hosts to better understand host-parasite co-evolution. Our research suggests that reported cases of schistosome-associated HGT may be due to technical artifacts as opposed to biological reality as we were unable to substantiate them. HGT clearly occurs in eukaryotic organisms, but the burden of proof is high and we emphasize the importance of multiple lines of evidence to conclusively document HGT. (C) 2015 Elsevier B.V. All rights reserved."
2,1,9,7,3,within an individuals lifespan (single generation),no spatial aspect,multiple species in the wild - environment changing,whole genome,both,Vignesh Venkatakrishnan,2015,https://doi.org/10.1038/ncomms8121,"Desjardins, CA; Sanscrainte, ND; Goldberg, JM; Heiman, D; Young, S; Zeng, QD; Madhani, HD; Becnel, JJ; Cuomo, CA",Contrasting host-pathogen interactions and genome evolution in two generalist and specialist microsporidian pathogens of mosquitoes,NATURE COMMUNICATIONS,6,,,7121,10.1038/ncomms8121,"Obligate intracellular pathogens depend on their host for growth yet must also evade detection by host defenses. Here we investigate host adaptation in two Microsporidia, the specialist Edhazardia aedis and the generalist Vavraia culicis, pathogens of disease vector mosquitoes. Genomic analysis and deep RNA-Seq across infection time courses reveal fundamental differences between these pathogens. E. aedis retains enhanced cell surface modification and signalling capacity, upregulating protein trafficking and secretion dynamically during infection. V. culicis is less dependent on its host for basic metabolites and retains a subset of spliceosomal components, with a transcriptome broadly focused on growth and replication. Transcriptional profiling of mosquito immune responses reveals that response to infection by E. aedis differs dramatically depending on the mode of infection, and that antimicrobial defensins may play a general role in mosquito defense against Microsporidia. This analysis illuminates fundamentally different evolutionary paths and host interplay of specialist and generalist pathogens."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Vignesh Venkatakrishnan,2015,https://doi.org/10.1016/j.resmic.2014.10.013,"Frey, J; Falquet, L",Patho-genetics of Clostridium chauvoei,RESEARCH IN MICROBIOLOGY,166,384,392,,10.1016/j.resmic.2014.10.013,"The genomic sequence of Clostridium chauvoei, the etiological agent of blackleg, a severe disease of ruminants with high mortality specified by a myonecrosis reveals a chromosome of 2.8 million base-pairs and a cryptic plasmid of 5.5 kilo base-pairs. The chromosome contains the main pathways like glycolysis/gluconeogenesis, sugar metabolism, purine and pyrimidine metabolisms, but the notable absence of genes of the citric acid cycle and deficient or partially deficient amino acid metabolism for Histidine, Tyrosine, Phenylalanine, and Tryptophan. These essential amino acids might be acquired from host tissue damage caused by various toxins and by protein metabolism that includes 57 genes for peptidases, and several ABC transporters for amino acids import. (C) 2014 The Authors."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Vignesh Venkatakrishnan,2015,https://doi.org/10.1074/mcp.M114.047373,"Croft, NP; de Verteuil, DA; Smith, SA; Wong, YC; Schittenhelm, RB; Tscharke, DC; Purcell, AW",Simultaneous Quantification of Viral Antigen Expression Kinetics Using Data-Independent (DIA) Mass Spectrometry,MOLECULAR & CELLULAR PROTEOMICS,14,1361,1372,,10.1074/mcp.M114.047373,"The generation of antigen-specific reagents is a significant bottleneck in the study of complex pathogens that express many hundreds to thousands of different proteins or to emerging or new strains of viruses that display potential pandemic qualities and therefore require rapid investigation. In these instances the development of antibodies for example can be prohibitively expensive to cover the full pathogen proteome, or the lead time may be unacceptably long in urgent cases where new highly pathogenic viral strains may emerge. Because genomic information on such pathogens can be rapidly acquired this opens up avenues using mass spectrometric approaches to study pathogen antigen expression, host responses and for screening the utility of therapeutics. In particular, data-independent acquisition (DIA) modalities on high-resolution mass spectrometers generate spectral information on all components of a complex sample providing depth of coverage hitherto only seen in genomic deep sequencing. The spectral information generated by DIA can be iteratively interrogated for potentially any protein of interest providing both evidence of protein expression and quantitation. Here we apply a solely DIA mass spectrometry based methodology to profile the viral antigen expression in cells infected with vaccinia virus up to 9 h post infection without the need for antigen specific antibodies or other reagents. We demonstrate deep coverage of the vaccinia virus proteome using a SWATH-MS acquisition approach, extracting quantitative kinetics of 100 virus proteins within a single experiment. The results highlight the complexity of vaccinia protein expression, complementing what is known at the transcriptomic level, and provide a valuable resource and technique for future studies of viral infection and replication kinetics. Furthermore, they highlight the utility of DIA and mass spectrometry in the dissection of host-pathogen interactions."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,both,Vignesh Venkatakrishnan,2015,https://doi.org/10.1186/s13071-015-0834-1,"Hebert, FO; Phelps, L; Samonte, I; Panchal, M; Grambauer, S; Barber, I; Kalbe, M; Landry, CR; Aubin-Horth, N",Identification of candidate mimicry proteins involved in parasite-driven phenotypic changes,PARASITES & VECTORS,8,,,225,10.1186/s13071-015-0834-1,"Background: Endoparasites with complex life cycles are faced with several biological challenges, as they need to occupy various ecological niches throughout their development. Host phenotypes that increase the parasite's transmission rate to the next host have been extensively described, but few mechanistic explanations have been proposed to describe their proximate causes. In this study we explore the possibility that host phenotypic changes are triggered by the production of mimicry proteins from the parasite by using an ecological model system consisting of the infection of the threespine stickleback (Gasterosteus aculeatus) by the cestode Schistocephalus solidus. Method: Using RNA-seq data, we assembled 9,093 protein-coding genes from which ORFs were predicted to generate a reference proteome. Based on a previously published method, we built two complementary analysis pipelines to i) establish a general classification of protein similarity among various species (pipeline A) and ii) identify candidate mimicry proteins showing specific host-parasite similarities (pipeline B), a key feature underlying the possibility of molecular mimicry. Results: Ninety-four tapeworm proteins showed high local sequence homology with stickleback proteins. Four of these candidates correspond to secreted or membrane proteins that could be produced by the parasite and eventually be released in or be in contact with the host to modulate physiological pathways involved in various phenotypes (e.g. behaviors). One of these candidates belongs to the Wnt family, a large group of signaling molecules involved in cell-to-cell interactions and various developmental pathways. The three other candidates are involved in ion transport and post-translational protein modifications. We further confirmed that these four candidates are expressed in three different developmental stages of the cestode by RT-PCR, including the stages found in the host. Conclusion: In this study, we identified mimicry candidate peptides from a behavior-altering cestode showing specific sequence similarity with host proteins. Despite their potential role in modulating host pathways that could lead to parasite-induced phenotypic changes and despite our confirmation that they are expressed in the developmental stage corresponding to the altered host behavior, further investigations will be needed to confirm their mechanistic role in the molecular cross-talk taking place between Schistocephalus solidus and the threespine stickleback."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,both,Vignesh Venkatakrishnan,2015,https://doi.org/10.1021/pr5010136,"Teichmann, A; Varsas, DM; Monteiro, KM; Menehetti, BV; Dutra, CS; Paredes, R; Galanti, N; Zaha, A; Ferreira, HB",Characterization of 14-3-3 Isoforms Expressed in the Echinococcus granulosus Pathogenic Larval Stage,JOURNAL OF PROTEOME RESEARCH,14,1700,1715,,10.1021/pr5010136,"The 14-3-3 protein family of eukaryotic regulators was studied in Echinococcus granulosus, the causative agent of cystic hydatid disease. These proteins mediate important cellular processes in eukaryotes and are expected to play important roles in parasite biology. Six isoforms of E. granulosus 14-3-3 genes and proteins (Eg14-3-3.1-6) were analyzed, and their phylogenetic relationships were established with bona fide 14-3-3 orthologous proteins from eukaryotic species. Eg14-3-3 isoforms with previous evidence of expression (Eg14-3-3.1-4) in E. granulosus pathogenic larval stage (metacestode) were cloned, and recombinant proteins were used for functional studies. These protein isoforms were detected in different components of E. granulosus metacestode, including interface components with the host. The roles that are played by Eg14-3-3 proteins in parasite biology were inferred from the repertoires of interacting proteins with each isoform, as assessed by gel overlay, cross-linking, and affinity chromatography assays. A total of 95 Eg14-3-3 protein ligands were identified by mass spectrometry. Eg14-3-3 isoforms have shared partners (44 proteins), indicating some overlapping functions; however, they also bind exclusive partners (51 proteins), suggesting Eg14-3-3 functional specialization. These ligand repertoires indicate the involvement of Eg14-3-3 proteins in multiple biochemical pathways in the E. granulosus metacestode and note some degree of isoform specialization."
4,1,3,6,5,many generations,no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,both,Vignesh Venkatakrishnan,2015,https://doi.org/10.1038/ismej.2014.242,"Connolly, JP; Goldstone, RJ; Burgess, K; Cogdell, RJ; Beatson, SA; Vollmer, W; Smith, DG; Roe, AJ",The host metabolite D-serine contributes to bacterial niche specificity through gene selection,ISME JOURNAL,9,1039,1051,,10.1038/ismej.2014.242,"Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host-pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an 'evolutionary incompatibility' between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity."
5,1,2,5,6,speciation time (small tree),no spatial aspect,single species laboratory system - no environmental aspect,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Vignesh Venkatakrishnan,2015,https://doi.org/10.1016/j.dci.2014.12.006,"Li, Y; Liu, SK; Qin, ZK; Yao, J; Jiang, C; Song, L; Dunham, R; Liu, ZJ","The serpin superfamily in channel catfish: Identification, phylogenetic analysis and expression profiling in mucosal tissues after bacterial infections",DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY,49,267,277,,10.1016/j.dci.2014.12.006,"The superfamily of serine protease inhibitors (serpins) are broadly distributed in all kingdoms of life. Serpins play critical roles in an array of fundamental biological processes. In this study, we identified a complete set of 25 serpin genes from channel catfish genome by comprehensive data mining of existing genomic resources. Phylogenetic analysis verified their identities and supported the classification of serpins into six families as in mammals. Extensive comparative genomic analyses suggested that most serpins were conserved among vertebrates, while some were lineage-specific. Analysis of serpin gene expression in mucosal tissues after bacterial infections indicated that serpin genes were regulated in a tissue-specific and time-dependent manner. Distinct expression patterns between infections of the two pathogens were observed, indicating that much more rapid host responses of serpin expression were initiated after ESC infection than after columnaris infection. These studies set the foundation for future studies of host-pathogen interactions. (C) 2014 Elsevier Ltd. All rights reserved."
1,1,3,7,2,none,no spatial aspect,single species laboratory system - environmental aspect present,whole genome,Pathogen,Vignesh Venkatakrishnan,2015,https://doi.org/10.3389/fmicb.2015.00204,"Hazen, TH; Lafon, PC; Garrett, NM; Lowe, TM; Silberger, DJ; Rowe, LA; Frace, M; Parsons, MB; Bopp, CA; Rasko, DA; Sobecky, PA",Insights into the environmental reservoir of pathogenic Vibrio parahaemolyticus using comparative genomics,FRONTIERS IN MICROBIOLOGY,6,,,204,10.3389/fmicb.2015.00204,"Vibrio parahaemolyticus is an aquatic halophilic bacterium that occupies estuarine and coastal marine environments, and is a leading cause of seafood-borne food poisoning cases. To investigate the environmental reservoir and potential gene flow that occurs among V. parahaemolyticus isolates, the virulence-associated gene content and genome diversity of a collection of 133 V. parahaemolyticus isolates were analyzed. Phylogenetic analysis of housekeeping genes, and pulsed-field gel electrophoresis, demonstrated that there is genetic similarity among V. parahaemolyticus clinical and environmental isolates. Whole-genome sequencing and comparative analysis of six representative V. parahaemolyticus isolates was used to identify genes that are unique to the clinical and environmental isolates examined. Comparative genomics demonstrated an O3:K6 environmental isolate, AF91, which was cultured from sediment collected in Florida in 2006, has significant genomic similarity to the post-1995 O3:K6 isolates. However, AF91 lacks the majority of the virulence-associated genes and genomic islands associated with these highly virulent post-1995 O3:K6 genomes. These findings demonstrate that although they do not contain most of the known virulence-associated regions, some V. parahaemolyticus environmental isolates exhibit significant genetic similarity to clinical isolates. This highlights the dynamic nature of the V. parahaemolyticus genome allowing them to transition between aquatic and host-pathogen states."
1,1,3,6,2,none,no spatial aspect,single species laboratory system - environmental aspect present,exome/transcriptome,Host,Vignesh Venkatakrishnan,2015,https://doi.org/10.1186/s13099-015-0052-6,"Rao, R; Zhu, YB; Alinejad, T; Tiruvayipati, S; Thong, KL; Wang, J; Bhassu, S",RNA-seq analysis of Macrobrachium rosenbergii hepatopancreas in response to Vibrio parahaemolyticus infection,GUT PATHOGENS,7,,,6,10.1186/s13099-015-0052-6,"Background: The Malaysian giant freshwater prawn, Macrobrachium rosenbergii, is an economically important crustacean worldwide. However, production of this prawn is facing a serious threat from Vibriosis disease caused by Vibrio species such as Vibrio parahaemolyticus. Unfortunately, the mechanisms involved in the immune response of this species to bacterial infection are not fully understood. We therefore used a high-throughput deep sequencing technology to investigate the transcriptome and comparative expression profiles of the hepatopancreas from this freshwater prawn infected with V. parahaemolyticus to gain an increased understanding of the molecular mechanisms underlying the species' immune response to this pathogenic bacteria. Result: A total of 59,122,940 raw reads were obtained from the control group, and 58,385,094 reads from the Vibrio-infected group. Via de novo assembly by Trinity assembler, 59,050 control unigenes and 73,946 Vibrio-infected group unigenes were obtained. By clustering unigenes from both libraries, a total of 64,411 standard unigenes were produced. The standard unigenes were annotated against the NCBI non-redundant, Swiss-Prot, Kyoto Encyclopaedia of Genes and Genome pathway (KEGG) and Orthologous Groups of Proteins (COG) databases, with 19,799 (30.73%), 16,832 (26.13%), 14,706 (22.83%) and 7,856 (12.19%) hits respectively, giving a final total of 22,455 significant hits (34.86% of all unigenes). A Gene Ontology (GO) analysis search using the Blast2GO program resulted in 6,007 unigenes (9.32%) being categorized into 55 functional groups. A differential gene expression analysis produced a total of 14,569 unigenes aberrantly expressed, with 11,446 unigenes significantly up-regulated and 3,103 unigenes significantly down-regulated. The differentially expressed immune genes fall under various processes of the animal immune system. Conclusion: This study provided an insight into the antibacterial mechanism in M. rosenbergii and the role of differentially expressed immune genes in response to V. parahaemolyticus infection. Furthermore, this study has generated an abundant list of transcript from M. rosenbergii which will provide a fundamental basis for future genomics research in this field."
2,1,4,6,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - no environmental aspect present,exome/transcriptome,both,Helena Westerdahl,2015,https://doi.org/10.1186/s12864-015-1319-5,"Hou, N; Piao, XY; Cai, PF; Wu, C; Liu, S; Xiao, Y; Chen, QJ",A novel Schistosoma japonicum endonuclease homologous to DNase II,BMC GENOMICS,16,,,126,10.1186/s12864-015-1319-5,"Background: Recent advances in studies of the Schistosoma japonicum genome have opened new avenues for the elucidation of parasite biology and the identification of novel targets for vaccines, drug development and early diagnostic tools. Results: In this study, we surveyed the S. japonicum genome database for genes encoding nucleases. A total of 130 nucleases of 3 classes were found. Transcriptional analysis of these genes using a genomic DNA microarray revealed that the majority of the nucleases were differentially expressed in parasites of different developmental stages or different genders, whereas no obvious transcriptional variation was detected in parasites from different hosts. Further analysis of the putative DNases of S. japonicum revealed a novel DNase II homologue (Sjda) that contained a highly conserved catalytic domain. A recombinant Sjda-GST protein efficiently hydrolysed genomic DNA in the absence of divalent iron. Western-blot and immunofluorescence assays showed that Sjda was mainly expressed on the teguments of female adult parasites and induced early humoral immune responses in infected mice. Conclusions: A novel DNase II homologue, Sjda, was identified in S. japonicum. Sjda was mainly distributed on the teguments of adult female parasites and possessed a typical divalent iron-independent DNA catalytic activity. This protein may play an important role in the host-parasite interaction."
1,1,6,3,2,none,no spatial aspect,single species in the wild - environment constant,gene family/microsatellites,Pathogen,Helena Westerdahl,2015,https://doi.org/10.3354/dao02833,"Hartikainen, H; Filippenko, D; Okamura, B; Vasemagi, A","First microsatellite loci of the myxozoan parasite Tetracapsuloides bryosalmonae, the causative agent of proliferative kidney disease (PKD)",DISEASES OF AQUATIC ORGANISMS,113,85,88,,10.3354/dao02833,"Proliferative kidney disease (PKD) caused by the myxozoan parasite Tetracapsuloides bryosalmonae is a severe parasitic disease of salmonid fish. Estimates of genetic variation in parasite populations across Europe are currently lacking. We developed the first polymorphic microsatellite markers for T. bryosalmonae using Illumina MiSeq sequence data derived from genomic DNA. Twelve polymorphic loci were identified from 24 tested loci. Allelic variation was low at most loci, ranging from 2 to 6 (average 3.0). The markers developed here are expected to be useful in future genetic studies of T. bryosalmonae, aimed at further understanding the dispersal of the parasite, host-parasite relationships and the epidemiology of PKD."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,both,Helena Westerdahl,2015,https://doi.org/10.3389/fimmu.2015.00023,"Casey, ME; Meade, KG; Nalpas, NC; Taraktsoglou, M; Browne, JA; Killick, KE; Park, SDE; Gormley, E; Hokamp, K; Magee, DA; MacHugh, DE",Analysis of the bovine monocyte-derived macrophage response to Mycobacterium avium subspecies paratuberculosis infection using RNA-seq,FRONTIERS IN IMMUNOLOGY,6,,,23,10.3389/fimmu.2015.00023,"Johne's disease, caused by infection with Mycobacterium avium subsp. paratuberculosis, (MAP), is a chronic intestinal disease of ruminants with serious economic consequences for cattle production in the United States and elsewhere. During infection, MAP bacilli are phagocytosed and subvert host macrophage processes, resulting in subclinical infections that can lead to immunopathology and dissemination of disease. Analysis of the host macrophage transcriptome during infection can therefore shed light on the molecular mechanisms and host-pathogen interplay associated with Johne's disease. Here, we describe results of an in vitro study of the bovine monocyte-derived macrophage (MDM) transcriptome response during MAP infection using RNA-seq. MDM were obtained from seven age- and sex-matched Holstein-Friesian cattle and were infected with MAP across a 6-h infection time course with non-infected controls. We observed 245 and 574 differentially expressed (DE) genes in MAP-infected versus non-infected control samples (adjusted P value <= 0.05) at 2 and 6 h post-infection, respectively. Functional analyses of these DE genes, including biological pathway enrichment, highlighted potential functional roles for genes that have not been previously described in the host response to infection with MAP bacilli. In addition, differential expression of pro- and anti-inflammatory cytokine genes, such as those associated with the 11,10 signaling pathway, and other immune-related genes that encode proteins involved in the bovine macrophage response to MAP infection emphasize the balance between protective host immunity and bacilli survival and proliferation. Systematic comparisons of RNA-seq gene expression results with Affymetrix (R) microarray data generated from the same experimental samples also demonstrated that RNA-seq represents a superior technology for studying host transcriptional responses to intracellular infection."
5,3,9,7,8,speciation time (small tree),small spatial scale (couple of populations),multiple species in the wild - environment changing,whole genome,Pathogen,Helena Westerdahl,2015,https://doi.org/10.1007/s00438-014-0900-y,"Ortiz, MF; Wallau, GL; Graichen, DAS; Loreto, ELS",An evaluation of the ecological relationship between Drosophila species and their parasitoid wasps as an opportunity for horizontal transposon transfer,MOLECULAR GENETICS AND GENOMICS,290,67,78,,10.1007/s00438-014-0900-y,"Evidences of horizontal transfer, the exchange of genetic material between reproductively isolated species, have accumulated over the last decades, including for multicellular eukaryotic organisms. However, the mechanisms and ecological relationships that promote such phenomenon is still poorly known. Host-parasite interaction is one type of relationship usually pointed in the literature that could potentially increase the probability of the horizontal transfer between species, because the species involved in such relationships are generally in close contact. Transposable elements, which are well-known genomic parasites, are DNA entities that tend to be involved in horizontal transfer due to their ability to mobilize between different genomic locations. Using Drosophila species and their parasitoid wasps as a host-parasite model, we evaluated the hypothesis that horizontal transposon transfers (HTTs) are more frequent in this set of species than in species that do not exhibit a close ecological and phylogenetic relationship. For this purpose, we sequenced two sets of species using a metagenomic and single-species genomic sampling approach through next-generation DNA sequencing. The first set was composed of five generalist Drosophila (D. maculifrons, D. bandeirantorum, D. polymorpha, D. mercatorum and D. willistoni) species and their associated parasitoid wasps, whereas the second set was composed of D. incompta, which is a flower specialist species, and its parasitoid wasp. We did not find strong evidence of HTT in the two sets of Drosophila and wasp parasites. However, at least five cases of HTT were observed between the generalist and specialist Drosophila species. Moreover, we detected an HT event involving a Wolbachia lineage between generalist and specialist species, indicating that these endosymbiotic bacteria could play a role as HTT vectors. In summary, our results do not support the hypothesis of prevalent HTT between species with a host-parasite relationship, at least for the studied wasp-Drosophila pairs. Moreover, it suggests that other mechanisms or parasites are involved in promoting HTT between Drosophila species as the Wolbachia endosymbiotic bacteria."
2,2,2,6,4,within an individuals lifespan (single generation),local (one population),single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Helena Westerdahl,2015,https://doi.org/10.4137/EBO.S25585,"Isewon, I; Oyelade, J; Brors, B; Adebiyi, E",In Silico Gene Regulatory Network of the Maurer's Cleft Pathway in Plasmodium falciparum,EVOLUTIONARY BIOINFORMATICS,11,231,238,,10.4137/EBO.S25585,"The Maurer's clefts (MCs) are very important for the survival of Plasmodium falciparum within an infected cell as they are induced by the parasite itself in the erythrocyte for protein trafficking. The MCs form an interesting part of the parasite's biology as they shed more light on how the parasite remodels the erythrocyte leading to host pathogenesis and death. Here, we predicted and analyzed the genetic regulatory network of genes identified to belong to the MCs using regularized graphical Gaussian model. Our network shows four major activators, their corresponding target genes, and predicted binding sites. One of these master activators is the serine repeat antigen 5 (SERA5), predominantly expressed among the SERA multigene family of P. falciparum, which is one of the blood-stage malaria vaccine candidates. Our results provide more details about functional interactions and the regulation of the genes in the MCs' pathway of P. falciparum."
5,3,6,7,8,speciation time (small tree),small spatial scale (couple of populations),single species in the wild - environment constant,whole genome,Pathogen,Helena Westerdahl,2015,https://doi.org/10.1093/nar/gku1271,"Kumar, N; Mariappan, V; Baddam, R; Lankapalli, AK; Shaik, S; Goh, KL; Loke, MF; Perkins, T; Benghezal, M; Hasnain, SE; Vadivelu, J; Marshall, BJ; Ahmed, N",Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution,NUCLEIC ACIDS RESEARCH,43,324,335,,10.1093/nar/gku1271,"The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host-pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner."
4,2,6,6,6,many generations,local (one population),single species in the wild - environment constant,exome/transcriptome,Pathogen,Helena Westerdahl,2015,https://doi.org/10.1016/j.ijmm.2014.10.005,"Windmuller, N; Witten, A; Block, D; Bunk, B; Sproer, C; Kahl, BC; Mellmann, A",Transcriptional adaptations during long-term persistence of Staphylococcus aureus in the airways of a cystic fibrosis patient,INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY,305,38,46,,10.1016/j.ijmm.2014.10.005,"The lungs of Cystic fibrosis (CF) patients are often colonized and/or infected by Staphylococcus aureus for years, mostly by one predominant clone. For long-term survival in this environment, S. aureus needs to adapt during its interactions with host factors, antibiotics, and other pathogens. Here, we study long-term transcriptional as well as genomic adaptations of an isogenic pair of S. aureus isolates from a single patient using RNA sequencing (RNA-Seq) and whole genome sequencing (WGS). Mimicking in vivo conditions, we cultivated the S. aureus isolates using artificial sputum medium before harvesting RNA for subsequent analysis. We confirmed our RNA-Seq data using quantitative real-time (qRT)-PCR and additionally investigated intermediate isolates from the same patient representing in total 13.2 years of persistence in the CF airways. Comparative RNA-Seq analysis of the first and the last (""late"") isolate revealed significant differences in the late isolate after 13.2 years of persistence. Of the 2545 genes expressed in both isolates that were cultivated aerobically, 256 genes were up- and 161 were down-regulated with a minimum 2-fold change (2f). Focusing on 25 highly (>= 80) up- (n= 9) or down- (n = 16) regulated genes, we identified several genes encoding for virulence factors involved in immune evasion, bacterial spread or secretion (e.g. spa, sak, and esxA). Moreover, these genes displayed similar expression trends under aerobic, microaerophilic and anaerobic conditions. Further qRT-PCR-experiments of highly up- or downregulated genes within intermediate S. aureus isolates resulted in different gene expression patterns over the years. Using sequencing analysis of the differently expressed genes and their upstream regions in the late S. aureus isolate resulted in only few genomic alterations. Comparative transcriptomic analysis revealed adaptive changes affecting mainly genes involved in host-pathogen interaction. Although the underlying mechanisms were not known, our results suggest adaptive processes beyond genomic mutations triggered by local factors rather than by activation of global regulators. (C) 2014 The Authors. Published by Elsevier GmbH."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Helena Westerdahl,2014,https://doi.org/10.1186/s12870-014-0376-2,"Almeida, NF; Leitao, ST; Krezdorn, N; Rotter, B; Winter, P; Rubiales, D; Patto, MCV","Allelic diversity in the transcriptomes of contrasting rust-infected genotypes of Lathyrus sativus, a lasting resource for smart breeding",BMC PLANT BIOLOGY,14,,,376,10.1186/s12870-014-0376-2,"Background: Grass pea (Lathyrus sativus L.) is a valuable resource for potentially durable partial resistance to rust. To gain insight into the resistance mechanism and identify potential resistance genes, we generated the first comprehensive transcriptome assemblies from control and Uromyces pisi inoculated leafs of a susceptible and a partially rust-resistant grass pea genotype by RNA-seq. Results: 134,914 contigs, shared by both libraries, were used to analyse their differential expression in response to rust infection. Functional annotation grouped 60.4% of the contigs present in plant databases (37.8% of total) to 33 main functional categories, being ""protein"", ""RNA"", ""signalling"", ""transport"" and ""stress"" the most represented. Transcription profiles revealed considerable differences in regulation of major phytohormone signalling pathways: whereas Salicylic and Abscisic Acid pathways were up-regulated in the resistant genotype, Jasmonate and Ethylene pathways were down-regulated in the susceptible one. As potential Resistance-genes we identified a mildew resistance locus O (MLO)-like gene, and MLO-related transcripts. Also, several pathogenesis-related genes were up-regulated in the resistant and exclusively down regulated in the susceptible genotype. Pathogen effectors identified in both inoculated libraries, as e.g. the rust Rtp1 transcript, may be responsible for the down-regulation of defence-related transcripts. The two genotypes contained 4,892 polymorphic contigs with SNPs unevenly distributed between different functional categories. Protein degradation (29.7%) and signalling receptor kinases (8.2%) were the most diverged, illustrating evolutionary adaptation of grass pea to the host/pathogens arms race. Conclusions: The vast array of novel, resistance-related genomic information we present here provides a highly valuable resource for future smart breeding approaches in this hitherto under-researched, valuable legume crop."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Helena Westerdahl,2014,https://doi.org/10.1371/journal.pone.0114960,"Kim, DK; Lillehoj, HS; Jang, SI; Lee, SH; Hong, YH; Cheng, HH",Transcriptional Profiles of Host-Pathogen Responses to Necrotic Enteritis and Differential Regulation of Immune Genes in Two Inbreed Chicken Lines Showing Disparate Disease Susceptibility,PLOS ONE,9,,,e114960,10.1371/journal.pone.0114960,"Necrotic enteritis (NE) is an important intestinal infectious disease of commercial poultry flocks caused by Clostridium perfringens. Using an experimental model of NE involving co-infection with C. perfringens and Eimeria maxima, transcriptome profiling and functional genomics approaches were applied to identify the genetic mechanisms that might regulate the host response to this disease. Microarray hybridization identified 1,049 transcripts whose levels were altered (601 increased, 448 decreased) in intestinal lymphocytes from C. perfringens/E. maxima co-infected Ross chickens compared with uninfected controls. Five biological functions, all related to host immunity and inflammation, and 11 pathways were identified from this dataset. To further elucidate the role of host genetics in NE susceptibility, two inbred chicken lines, ADOL line 6 and line 7 which share an identical B-2 major histocompatibility complex haplotype but differ in their susceptibility to virus infection, were compared for clinical symptoms and the expression levels of a panel of immune-related genes during experimental NE. Line 6 chickens were more susceptible to development of experimental NE compared with line 7, as revealed by decreased body weight gain and increased E. maxima oocyst shedding. Of 21 immune-related genes examined, 15 were increased in C. perfringens/E. maxima co-infected line 6 vs. line 7 chickens. These results suggest that immune pathways are activated in response to experimental NE infection and that genetic determinants outside of the chicken B complex influence resistance to this disease."
1,2,6,7,3,none,local (one population),single species in the wild - environment constant,whole genome,Pathogen,Helena Westerdahl,2014,https://doi.org/10.1093/gbe/evu247,"Yang, YL; Xiong, J; Zhou, ZG; Huo, FM; Miao, W; Ran, C; Liu, YC; Zhang, JY; Feng, JM; Wang, M; Wang, M; Wang, L; Yao, B",The Genome of the Myxosporean Thelohanellus kitauei Shows Adaptations to Nutrient Acquisition within Its Fish Host,GENOME BIOLOGY AND EVOLUTION,6,3182,3198,,10.1093/gbe/evu247,"Members of Myxozoa, a parasitic metazoan taxon, have considerable detrimental effects on fish hosts and also have been associated with human food-borne illness. Little is known about their biology and metabolism. Analysis of the genome of Thelohanellus kitauei and comparative analysis with genomes of its two free-living cnidarian relatives revealed that T. kitauei has adapted to parasitism, as indicated by the streamlined metabolic repertoire and the tendency toward anabolism rather than catabolism. Thelohanellus kitauei mainly secretes proteases and protease inhibitors for nutrient digestion (parasite invasion), and depends on endocytosis (mainly low-density lipoprotein receptors-mediated type) and secondary carriers for nutrient absorption. Absence of both classic and complementary anaerobic pathways and gluconeogenesis, the lack of de novo synthesis and reduced activity in hydrolysis of fatty acids, amino acids, and nucleotides indicated that T. kitauei in this vertebrate host-parasite system has adapted to inhabit a physiological environment extremely rich in both oxygen and nutrients (especially glucose), which is consistent with its preferred parasitic site, that is, the host gut submucosa. Taking advantage of the genomic and transcriptomic information, 23 potential nutrition-related T. kitauei-specific chemotherapeutic targets were identified. This first genome sequence of a myxozoan will facilitate development of potential therapeutics for efficient control of myxozoan parasites and ultimately prevent myxozoan-induced fish-borne illnesses in humans."
2,1,5,2,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - environmental aspect present,full gene/regulator,Pathogen,Helena Westerdahl,2014,https://doi.org/10.1111/mmi.12819,"Ferreira, TR; Alves-Ferreira, EVC; Defina, TPA; Walrad, P; Papadopoulou, B; Cruz, AK",Altered expression of an RBP-associated arginine methyltransferase 7 in Leishmania major affects parasite infection,MOLECULAR MICROBIOLOGY,94,1085,1102,,10.1111/mmi.12819,"Protein arginine methylation is a widely conserved post-translational modification performed by arginine methyltransferases (PRMTs). However, its functional role in parasitic protozoa is still under-explored. The Leishmania major genome encodes five PRMT homologs, including PRMT7. Here we show that LmjPRMT7 expression and arginine monomethylation are tightly regulated in a lifecycle stage-dependent manner. LmjPRMT7 levels are higher during the early promastigote logarithmic phase, negligible at stationary and late-stationary phases and rise once more post-differentiation to intracellular amastigotes. Immunofluorescence and co-immunoprecipitation studies demonstrate that LmjPRMT7 is a cytosolic protein associated with several RNA-binding proteins (RBPs) from which Alba20 is monomethylated only in LmjPRMT7-expressing promastigote stages. In addition, Alba20 protein levels are significantly altered in stationary promastigotes of the LmjPRMT7 knockout mutant. Considering RBPs are well-known mammalian PRMT substrates, our data suggest that arginine methylation via LmjPRMT7 may modulate RBP function during Leishmania spp. lifecycle progression. Importantly, genomic deletion of the LmjPRMT7 gene leads to an increase in parasite infectivity both in vitro and in vivo, while lesion progression is significantly reduced in LmjPRMT7-overexpressing parasites. This study is the first to describe a role of Leishmania protein arginine methylation in host-parasite interactions."
6,3,8,7,9,speciation time (large tree),small spatial scale (couple of populations),multiple species in the wild - environment constant,whole genome,Pathogen,Helena Westerdahl,2014,https://doi.org/10.1073/pnas.1412662111,"Hu, X; Xiao, GH; Zheng, P; Shang, YF; Su, Y; Zhang, XY; Liu, XZ; Zhan, S; St Leger, RJ; Wang, CS",Trajectory and genomic determinants of fungal-pathogen speciation and host adaptation,PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,111,16796,16801,,10.1073/pnas.1412662111,"Much remains unknown regarding speciation. Host-pathogen interactions are a major driving force for diversification, but the genomic basis for speciation and host shifting remains unclear. The fungal genus Metarhizium contains species ranging from specialists with very narrow host ranges to generalists that attack a wide range of insects. By genomic analyses of seven species, we demonstrated that generalists evolved from specialists via transitional species with intermediate host ranges and that this shift paralleled insect evolution. We found that specialization was associated with retention of sexuality and rapid evolution of existing protein sequences whereas generalization was associated with protein-family expansion, loss of genome-defense mechanisms, genome restructuring, horizontal gene transfer, and positive selection that accelerated after reinforcement of reproductive isolation. These results advance understanding of speciation and genomic signatures that underlie pathogen adaptation to hosts."
2,1,6,6,3,within an individuals lifespan (single generation),no spatial aspect,single species in the wild - environment constant,exome/transcriptome,both,Helena Westerdahl,2014,https://doi.org/10.1016/j.molbiopara.2014.11.001,"Tritten, L; O'Neill, M; Nutting, C; Wanji, S; Njouendoui, A; Fombad, F; Kengne-Ouaffo, J; Mackenzie, C; Geary, T",Loa loa and Onchocerca ochengi miRNAs detected in host circulation,MOLECULAR AND BIOCHEMICAL PARASITOLOGY,198,14,17,,10.1016/j.molbiopara.2014.11.001,"A combination of deep-sequencing and bioinformatics analysis enabled identification of twenty-two microRNA candidates of potential nematode origin in plasma from Loa boo-infected baboons and a further ten from the plasma of an Onchocerca ochengi-infected cow. The obtained data were compared to results from previous work on miRNA candidates from Dirofilaria immitis and O. volvu/us found in host circulating blood, to examine the species specificity of the released miRNA. None of the miRNA candidates was found to be present in all four host-parasite scenarios and most of them were specific to only one of them. Eight candidate miRNAs were found to be identical in the full sequence in at least two different infections, while nine candidate miRNAs were found to be similar but not identical in at least four filarial species. (C) 2014 Elsevier B.V. All rights reserved."
5,1,1,3,6,speciation time (small tree),no spatial aspect,none - theoretical,gene family/microsatellites,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1603/ME13218,"Sweet, AD; Allen, JM; Johnson, KP",Novel Primers From Informative Nuclear Loci for Louse Molecular Phylogenetics (Insecta: Phthiraptera),JOURNAL OF MEDICAL ENTOMOLOGY,51,1122,1126,,10.1603/ME13218,"While parasitic lice (Insecta: Phthiraptera) have historically been an important model taxon for understanding host-parasite coevolution, very few molecular markers have been developed for phylogenetic analysis. The current markers are insufficient to resolve many of the deeper nodes in this group; therefore, sequences from additional genetic loci are necessary. Here, we design primers targeting several nuclear protein coding genes based on a complete genome and transcriptome of Pediculus humanus L. plus transcriptomes and modest coverage genomic data from five genera of avian feather lice. These primers were tested on 32 genera of avian feather lice (Ischnocera), including multiple species within some genera. All of the new primer combinations produced sequences for the majority of the genera and had similar or higher divergences than the most widely used nuclear protein-coding gene in lice, EF-1 alpha. These results indicate that these new loci will be useful in resolving phylogenetic relationships among parasitic lice."
5,1,1,7,6,speciation time (small tree),no spatial aspect,none - theoretical,whole genome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1128/mBio.02020-14,"Rahman, SA; Singh, Y; Kohli, S; Ahmad, J; Ehtesham, NZ; Tyagi, AK; Hasnain, SE","Comparative Analyses of Nonpathogenic, Opportunistic, and Totally Pathogenic Mycobacteria Reveal Genomic and Biochemical Variabilities and Highlight the Survival Attributes of Mycobacterium tuberculosis",MBIO,5,,,e02020-14,10.1128/mBio.02020-14,"Mycobacterial evolution involves various processes, such as genome reduction, gene cooption, and critical gene acquisition. Our comparative genome size analysis of 44 mycobacterial genomes revealed that the nonpathogenic (NP) genomes were bigger than those of opportunistic (OP) or totally pathogenic (TP) mycobacteria, with the TP genomes being smaller yet variable in size-their genomic plasticity reflected their ability to evolve and survive under various environmental conditions. From the 44 mycobacterial species, 13 species, representing TP, OP, and NP, were selected for genomic-relatedness analyses. Analysis of homologous protein-coding genes shared between Mycobacterium indicus pranii (NP), Mycobacterium intracellulare ATCC 13950 (OP), and Mycobacterium tuberculosis H37Rv (TP) revealed that 4,995 (i.e., similar to 95%) M. indicaus pranii proteins have homology with M. intracellulare, whereas the homologies among M. indicus pranii, M. intracellulare ATCC 13950, and M. tuberculosis H37Rv were significantly lower. A total of 4,153 (similar to 79%) M. indicus pranii proteins and 4,093 (similar to 79%) M. intracellulare ATCC 13950 proteins exhibited homology with the M. tuberculosis H37Rv proteome, while 3,301 (similar to 82%) and 3,295 (similar to 82%) M. tuberculosis H37Rv proteins showed homology with M. indicus pranii and M. intracellulare ATCC 13950 proteomes, respectively. Comparative metabolic pathway analyses of TP/OP/NP mycobacteria showed enzymatic plasticity between M. indicus pranii (NP) and M. intracellulare ATCC 13950 (OP), Mycobacterium avium 104 (OP), and M. tuberculosis H37Rv (TP). Mycobacterium tuberculosis seems to have acquired novel alternate pathways with possible roles in metabolism, host-pathogen interactions, virulence, and intracellular survival, and by implication some of these could be potential drug targets. IMPORTANCE The complete sequence analysis of Mycobacterium indicus pranii, a novel species of Mycobacterium shown earlier to have strong immunomodulatory properties and currently in use for the treatment of leprosy, places it evolutionarily at the point of transition to pathogenicity. With the purpose of establishing the importance of M. indicus pranii in providing insight into the virulence mechanism of tuberculous and nontuberculous mycobacteria, we carried out comparative genomic and proteomic analyses of 44 mycobacterial species representing nonpathogenic (NP), opportunistic (OP), and totally pathogenic (TP) mycobacteria. Our results clearly placed M. indicus pranii as an ancestor of the M. avium complex. Analyses of comparative metabolic pathways between M. indicus pranii (NP), M. tuberculosis (TP), and M. intracellulare (OP) pointed to the presence of novel alternative pathways in M. tuberculosis with implications for pathogenesis and survival in the human host and identification of new drug targets."
5,1,4,7,6,speciation time (small tree),no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1186/1471-2164-15-S6-S17,"Khiabanian, H; Carpenter, Z; Kugelman, J; Chan, J; Trifonov, V; Nagle, E; Warren, T; Iversen, P; Bavari, S; Palacios, G; Rabadan, R",Viral diversity and clonal evolution from unphased genomic data,BMC GENOMICS,15,,,S17,10.1186/1471-2164-15-S6-S17,"Background: Clonal expansion is a process in which a single organism reproduces asexually, giving rise to a diversifying population. It is pervasive in nature, from within-host pathogen evolution to emergent infectious disease outbreaks. Standard phylogenetic tools rely on full-length genomes of individual pathogens or population consensus sequences (phased genotypes). Although high-throughput sequencing technologies are able to sample population diversity, the short sequence reads inherent to them preclude assessing whether two reads originate from the same clone (unphased genotypes). This obstacle severely limits the application of phylogenetic methods and investigation of within-host dynamics of acute infections using this rich data source. Methods: We introduce two measures of diversity to study the evolution of clonal populations using unphased genomic data, which eliminate the need to construct full-length genomes. Our method follows a maximum likelihood approach to estimate evolutionary rates and times to the most recent common ancestor, based on a relaxed molecular clock model; independent of a growth model. Deviations from neutral evolution indicate the presence of selection and bottleneck events. Results: We evaluated our methods in silico and then compared it against existing approaches with the well-characterized 2009 H1N1 influenza pandemic. We then applied our method to high-throughput genomic data from marburgvirus-infected non-human primates and inferred the time of infection and the intra-host evolutionary rate, and identified purifying selection in viral populations. Conclusions: Our method has the power to make use of minor variants present in less than 1% of the population and capture genomic diversification within days of infection, making it an ideal tool for the study of acute RNA viral infection dynamics."
1,3,7,3,4,none,small spatial scale (couple of populations),single species in the wild - environment changing,gene family/microsatellites,Host,Jamie Winternitz,2014,https://doi.org/10.1016/j.meegid.2014.06.019,"Grzeskowiak, L; Stephan, W; Rose, LE",Epistatic selection and coadaptation in the Prf resistance complex of wild tomato,INFECTION GENETICS AND EVOLUTION,27,456,471,,10.1016/j.meegid.2014.06.019,"Natural selection imposed by pathogens is a strong and pervasive evolutionary force structuring genetic diversity within their hosts' genomes and populations. As a model system for understanding the genomic impact of host-parasite coevolution, we have been studying the evolutionary dynamics of disease resistance genes in wild relatives of the cultivated tomato species. In this study, we investigated the sequence variation and evolutionary history of three linked genes involved in pathogen resistance in populations of Solanum peruvianum (Pto, Fen, and Prf). These genes encode proteins, which form a multimeric complex and together activate defense responses. We used standard linkage disequilibrium, as well as partitioning of linkage disequilibrium components across populations and correlated substitution analysis to identify amino acid positions that are candidates for coevolving sites between Pto/Fen and Prf. These candidates were mapped onto known and predicted structures of Pto, Fen and Prf to visualize putative coevolving regions between proteins. We discuss the functional significance of these coevolving pairs in the context of what is known from previous structure-function studies of Pto, Fen and Prf. (C) 2014 Elsevier B.V. All rights reserved."
6,1,4,7,7,speciation time (large tree),no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1371/journal.pcbi.1003907,"Lindgreen, S; Umu, SU; Lai, ASW; Eldai, H; Liu, WT; McGimpsey, S; Wheeler, NE; Biggs, PJ; Thomson, NR; Barquist, L; Poole, AM; Gardner, PP",Robust Identification of Noncoding RNA from Transcriptomes Requires Phylogenetically-Informed Sampling,PLOS COMPUTATIONAL BIOLOGY,10,,,e1003907,10.1371/journal.pcbi.1003907,"Noncoding RNAs are integral to a wide range of biological processes, including translation, gene regulation, host-pathogen interactions and environmental sensing. While genomics is now a mature field, our capacity to identify noncoding RNA elements in bacterial and archaeal genomes is hampered by the difficulty of de novo identification. The emergence of new technologies for characterizing transcriptome outputs, notably RNA-seq, are improving noncoding RNA identification and expression quantification. However, a major challenge is to robustly distinguish functional outputs from transcriptional noise. To establish whether annotation of existing transcriptome data has effectively captured all functional outputs, we analysed over 400 publicly available RNA-seq datasets spanning 37 different Archaea and Bacteria. Using comparative tools, we identify close to a thousand highly-expressed candidate noncoding RNAs. However, our analyses reveal that capacity to identify noncoding RNA outputs is strongly dependent on phylogenetic sampling. Surprisingly, and in stark contrast to protein-coding genes, the phylogenetic window for effective use of comparative methods is perversely narrow: aggregating public datasets only produced one phylogenetic cluster where these tools could be used to robustly separate unannotated noncoding RNAs from a null hypothesis of transcriptional noise. Our results show that for the full potential of transcriptomics data to be realized, a change in experimental design is paramount: effective transcriptomics requires phylogeny-aware sampling."
1,1,4,7,2,none,no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,both,Jamie Winternitz,2014,https://doi.org/10.1534/genetics.114.165498,"Leichty, AR; Brisson, D",Selective Whole Genome Amplification for Resequencing Target Microbial Species from Complex Natural Samples,GENETICS,198,473,U35,,10.1534/genetics.114.165498,"Population genomic analyses have demonstrated power to address major questions in evolutionary and molecular microbiology. Collecting populations of genomes is hindered in many microbial species by the absence of a cost effective and practical method to collect ample quantities of sufficiently pure genomic DNA for next-generation sequencing. Here we present a simple method to amplify genomes of a target microbial species present in a complex, natural sample. The selective whole genome amplification (SWGA) technique amplifies target genomes using nucleotide sequence motifs that are common in the target microbe genome, but rare in the background genomes, to prime the highly processive phi29 polymerase. SWGA thus selectively amplifies the target genome from samples in which it originally represented a minor fraction of the total DNA. The post-SWGA samples are enriched in target genomic DNA, which are ideal for population resequencing. We demonstrate the efficacy of SWGA using both laboratory-prepared mixtures of cultured microbes as well as a natural host-microbe association. Targeted amplification of Borrelia burgdorferi mixed with Escherichia coli at genome ratios of 1:2000 resulted in >10(5)-fold amplification of the target genomes with <6.7-fold amplification of the background. SWGA-treated genomic extracts from Wolbachia pipientis-infected Drosophila melanogaster resulted in up to 70% of high-throughput resequencing reads mapping to the W. pipientis genome. By contrast, 2-9% of sequencing reads were derived from W. pipientis without prior amplification. The SWGA technique results in high sequencing coverage at a fraction of the sequencing effort, thus allowing population genomic studies at affordable costs."
5,1,4,7,6,speciation time (small tree),no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1101/gr.168955.113,"Reid, AJ; Blake, DP; Ansari, HR; Billington, K; Browne, HP; Bryant, J; Dunn, M; Hung, SS; Kawahara, F; Miranda-Saavedra, D; Malas, TB; Mourier, T; Naghra, H; Nair, M; Otto, TD; Rawlings, ND; Rivailler, P; Sanchez-Flores, A; Sanders, M; Subramaniam, C; Tay, YL; Woo, Y; Wu, XK; Barrell, B; Dear, PH; Doerig, C; Gruber, A; Ivens, AC; Parkinson, J; Rajandream, MA; Shirley, MW; Wan, KL; Berriman, M; Tomley, FM; Pain, A",Genomic analysis of the causative agents of coccidiosis in domestic chickens,GENOME RESEARCH,24,1676,1685,,10.1101/gr.168955.113,"Global production of chickens has trebled in the past two decades and they are now the most important source of dietary animal protein worldwide. Chickens are subject to many infectious diseases that reduce their performance and productivity. Coccidiosis, caused by apicomplexan protozoa of the genus Eimeria, is one of the most important poultry diseases. Understanding the biology of Eimeria parasites underpins development of new drugs and vaccines needed to improve global food security. We have produced annotated genome sequences of all seven species of Eimeria that infect domestic chickens, which reveal the full extent of previously described repeat-rich and repeat-poor regions and show that these parasites possess the most repeat-rich proteomes ever described. Furthermore, while no other apicomplexan has been found to possess retrotransposons, Eimeria is home to a family of chromoviruses. Analysis of Eimeria genes involved in basic biology and host-parasite interaction highlights adaptations to a relatively simple developmental life cycle and a complex array of co-expressed surface proteins involved in host cell binding."
1,1,2,5,2,none,no spatial aspect,single species laboratory system - no environmental aspect,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Jamie Winternitz,2014,https://doi.org/10.1007/s11032-014-0118-z,"Oblessuc, PR; Baroni, RM; Pereira, GD; Chiorato, AF; Carbonell, SAM; Brinez, B; Silva, LDE; Garcia, AAF; Camargo, LEA; Kelly, JD; Benchimol-Reis, LL",Quantitative analysis of race-specific resistance to Colletotrichum lindemuthianum in common bean,MOLECULAR BREEDING,34,1313,1329,,10.1007/s11032-014-0118-z,"Molecular genetic maps continue to play a major role in breeding of crop species. The common bean genetic map of the recombinant inbred line population IAC-UNA x CAL 143 (UC) has been used to detect loci controlling important agronomic traits in common bean. In the current study, new microsatellite markers were added to the UC map and the linkage analysis was refined using current genomic resources of common bean, in order to identify quantitative resistance loci (QRL) associated with different races of the anthracnose pathogen. A single race inoculation was conducted in greenhouse using four plants per plot. Both race-specific and joint-adjusted disease severity means, obtained from linear-mixed model, were used to perform multiple interval mapping (MIM) and multi-trait MIM (MTMIM). In total, 13 and 11 QRL were identified by MIM and MTMIM analyses, respectively; with nine being observed in both analyses. ANT02.1(UC) and ANT07.1(UC) showed major effects on resistance both for MIM and MTMIM. Common major QRL for resistance to the three anthracnose races were expected, since high genetic pairwise-correlation was observed between the race-specific and joint-adjusted disease severity means. Therewith, both ANT02.1 and ANT07.1 can be regarded as valuable targets for marker-assisted selection; and so, putative genes potentially involved in the resistance response were identified in these QRL regions. Minor effect QRL were also observed, showing differential affects either on race-specific or multi-trait analyses and may play a role on durable horizontal resistance. These results contribute to a better understanding of the host-pathogen interaction and to breeding for enhancing resistance to Colletotrichum lindemuthianum in common bean."
5,4,9,1,9,speciation time (small tree),species range,multiple species in the wild - environment changing,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Jamie Winternitz,2014,https://doi.org/10.1073/pnas.1403255111,"Eastwood, JR; Berg, ML; Ribot, RFH; Raidal, SR; Buchanan, KL; Walder, KR; Bennett, ATD",Phylogenetic analysis of beak and feather disease virus across a host ring-species complex,PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,111,14153,14158,,10.1073/pnas.1403255111,"Pathogens have been hypothesized to play a major role in host diversity and speciation. Susceptibility of hybrid hosts to pathogens is thought to be a common phenomenon that could promote host population divergence and subsequently speciation. However, few studies have tested for pathogen infection across animal hybrid zones while testing for codivergence of the pathogens in the hybridizing host complex. Over 8 y, we studied natural infection by a rapidly evolving single-strand DNA virus, beak and feather diseases virus (BFDV), which infects parrots, exploiting a host-ring species complex (Platycercus elegans) in Australia. We found that host subspecies and their hybrids varied strikingly in both BFDV prevalence and load: both hybrid and phenotypically intermediate subspecies had lower prevalence and load compared with parental subspecies, while controlling for host age, sex, longitude and latitude, as well as temporal effects. We sequenced viral isolates throughout the range, which revealed patterns of genomic variation analogous to Mayr's ring-species hypothesis, to our knowledge for the first time in any host-pathogen system. Viral phylogeny, geographic location, intraspecific host density, and parrot community diversity and composition did not explain the differences in BFDV prevalence or load between subpopulations. Overall, our analyses suggest that functional host responses to infection, or force of infection, differ between subspecies and hybrids. Our findings highlight the role of host hybridization and clines in altering host-pathogen interactions, dynamics that can have important implications for models of speciation with gene flow, and offer insights into how pathogens may adapt to diverging host populations."
1,1,2,6,2,none,no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1128/mBio.01727-14,"Brown, NF; Rogers, LD; Sanderson, KL; Gouw, JW; Hartland, EL; Foster, LJ",A Horizontally Acquired Transcription Factor Coordinates Salmonella Adaptations to Host Microenvironments,MBIO,5,,,e01727-14,10.1128/mBio.01727-14,"The transcription factors HilA and SsrB activate expression of two type III secretion systems (T3SSs) and cognate effectors that reprogram host cell functions to benefit infecting Salmonella in the host. These transcription factors, the secretion systems, and the effectors are all encoded by horizontally acquired genes. Using quantitative proteomics, we quantified the abundance of 2,149 proteins from hilA or ssrB Salmonella in vitro. Our results suggest that the HilA regulon does not extend significantly beyond proteins known to be involved in direct interactions with intestinal epithelium. On the other hand, SsrB influences the expression of a diverse range of proteins, many of which are ancestral to the acquisition of ssrB. In addition to the known regulon of T3SS-related proteins, we show that, through SodCI and bacterioferritin, SsrB controls resistance to reactive oxygen species and that SsrB down-regulates flagella and motility. This indicates that SsrB-controlled proteins not only redirect host cell membrane traffic to establish a supportive niche within host cells but also have adapted to the chemistry and physical constraints of that niche. IMPORTANCE Expression of T3SSs typically requires a transcription factor that is linked in a genomic island. Studies of the targets of HilA and SsrB have focused on almost exclusively on T3SS substrates that are either linked or encoded in distinct genomic islands. By broadening our focus, we found that the regulon of SsrB extended considerably beyond T3SS-2 and its substrates, while that of HilA did not. That at least two SsrB-regulated processes streamline existence in the intracellular niche afforded by T3SS-2 seems to be a predictable outcome of evolution and natural selection. However, and importantly, these are the first such functions to be implicated as being SsrB dependent. The concept of T3SS-associated transcription factors coordinating manipulations of host cells together with distinct bacterial processes for increased efficiency has unrealized implications for numerous host-pathogen systems."
5,3,7,7,8,speciation time (small tree),small spatial scale (couple of populations),single species in the wild - environment changing,whole genome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1128/mBio.01974-14,"Lamelas, A; Harris, SR; Roltgen, K; Dangy, JP; Hauser, J; Kingsley, RA; Connor, TR; Sie, A; Hodgson, A; Dougan, G; Parkhill, J; Bentley, SD; Pluschke, G",Emergence of a New Epidemic Neisseria meningitidis Serogroup A Clone in the African Meningitis Belt: High-Resolution Picture of Genomic Changes That Mediate Immune Evasion,MBIO,5,,,e01974-14,10.1128/mBio.01974-14,"In the African ""meningitis belt,"" outbreaks of meningococcal meningitis occur in cycles, representing a model for the role of host-pathogen interactions in epidemic processes. The periodicity of the epidemics is not well understood, nor is it currently possible to predict them. In our longitudinal colonization and disease surveys, we have observed waves of clonal replacement with the same serogroup, suggesting that immunity to noncapsular antigens plays a significant role in natural herd immunity. Here, through comparative genomic analysis of 100 meningococcal isolates, we provide a high-resolution view of the evolutionary changes that occurred during clonal replacement of a hypervirulent meningococcal clone (ST-7) by a descendant clone (ST-2859). We show that the majority of genetic changes are due to homologous recombination of laterally acquired DNA, with more than 20% of these events involving acquisition of DNA from other species. Signals of adaptation to evade herd immunity were indicated by genomic hot spots of recombination. Most striking is the high frequency of changes involving the pgl locus, which determines the glycosylation patterns of major protein antigens. High-frequency changes were also observed for genes involved in the regulation of pilus expression and the synthesis of Maf3 adhesins, highlighting the importance of these surface features in host-pathogen interaction and immune evasion. IMPORTANCE While established meningococcal capsule polysaccharide vaccines are protective through the induction of anticapsular antibodies, findings of our longitudinal studies in the African meningitis belt have indicated that immunity to noncapsular antigens plays a significant role in natural herd immunity. Our results show that meningococci evade herd immunity through the rapid homologous replacement of just a few key genomic loci that affect noncapsular cell surface components. Identification of recombination hot spots thus represents an eminent approach to gain insight into targets of protective natural immune responses. Moreover, our results highlight the role of the dynamics of the protein glycosylation repertoire in immune evasion by Neisseria meningitidis. These results have major implications for the design of next-generation protein-based subunit vaccines."
5,3,7,7,8,speciation time (small tree),small spatial scale (couple of populations),single species in the wild - environment changing,whole genome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1128/mBio.01592-14,"Markussen, T; Marvig, RL; Gomez-Lozano, M; Aanaes, K; Burleigh, AE; Hoiby, N; Johansen, HK; Molin, S; Jelsbak, L",Environmental Heterogeneity Drives Within-Host Diversification and Evolution of Pseudomonas aeruginosa,MBIO,5,,,e01592-14,10.1128/mBio.01592-14,"Microbial population polymorphisms are commonly observed in natural environments, including long-term infected hosts. However, the underlying processes promoting and stabilizing diversity are difficult to unravel and are not well understood. Here, we use chronic infection of cystic fibrosis airways by the opportunistic pathogen Pseudomonas aeruginosa as a system for investigating bacterial diversification processes during the course of infection. We analyze clonal bacterial isolates sampled during a 32-year period and map temporal and spatial variations in population diversity to different infection sites within the infected host. We show that the ancestral infecting strain diverged into distinct sublineages, each with their own functional and genomic signatures and rates of adaptation, immediately after initial colonization. The sublineages coexisted in the host for decades, suggesting rapid evolution of stable population polymorphisms. Critically, the observed generation and maintenance of population diversity was the result of partitioning of the sublineages into physically separated niches in the CF airway. The results reveal a complex within-host population structure not previously realized and provide evidence that the heterogeneity of the highly structured and complex host environment promotes the evolution and long-term stability of pathogen population diversity during infection. IMPORTANCE Within-host pathogen evolution and diversification during the course of chronic infections is of importance in relation to therapeutic intervention strategies, yet our understanding of these processes is limited. Here, we investigate intraclonal population diversity in P. aeruginosa during chronic airway infections in cystic fibrosis patients. We show the evolution of a diverse population structure immediately after initial colonization, with divergence into multiple distinct sublineages that coexisted for decades and occupied distinct niches. Our results suggest that the spatial heterogeneity in CF airways plays a major role in relation to the generation and maintenance of population diversity and emphasize that a single isolate in sputum may not represent the entire pathogen population in the infected individual. A more complete understanding of the evolution of distinct clonal variants and their distribution in different niches could have positive implications for efficient therapy."
6,1,1,7,7,speciation time (large tree),no spatial aspect,none - theoretical,whole genome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.3389/fpls.2014.00372,"Sperschneider, J; Ying, H; Dodds, PN; Gardiner, DM; Upadhyaya, NM; Singh, KB; Manners, JM; Taylor, JM",Diversifying selection in the wheat stem rust fungus acts predominantly on pathogen-associated gene families and reveals candidate effectors,FRONTIERS IN PLANT SCIENCE,5,,,372,10.3389/fpls.2014.00372,"Plant pathogens cause severe losses to crop plants and threaten global food production. One striking example is the wheat stem rust fungus, Puccinia graminis f. sp. tritici, which can rapidly evolve new virulent pathotypes in response to resistant host lines. Like several other filamentous fungal and oomycete plant pathogens, its genome features expanded gene families that have been implicated in host-pathogen interactions, possibly encoding effector proteins that interact directly with target host defense proteins. Previous efforts to understand virulence largely relied on the prediction of secreted, small and cysteine-rich proteins as candidate effectors and thus delivered an overwhelming number of candidates. Here, we implement an alternative analysis strategy that uses the signal of adaptive evolution as a line of evidence for effector function, combined with comparative information and expression data. We demonstrate that in planta up-regulated genes that are rapidly evolving are found almost exclusively in pathogen-associated gene families, affirming the impact of host-pathogen co-evolution on genome structure and the adaptive diversification of specialized gene families. In particular, we predict 42 effector candidates that are conserved only across pathogens, induced during infection and rapidly evolving. One of our top candidates has recently been shown to induce genotype-specific hypersensitive cell death in wheat. This shows that comparative genomics incorporating the evolutionary signal of adaptation is powerful for predicting effector candidates for laboratory verification. Our system can be applied to a wide range of pathogens and will give insight into host-pathogen dynamics, ultimately leading to progress in strategies for disease control."
5,3,1,7,8,speciation time (small tree),small spatial scale (couple of populations),none - theoretical,whole genome,Pathogen,Jamie Winternitz,2014,https://doi.org/10.1038/ncomms5754,"Otto, TD; Rayner, JC; Bohme, U; Pain, A; Spottiswoode, N; Sanders, M; Quail, M; Ollomo, B; Renaud, F; Thomas, AW; Prugnolle, F; Conway, DJ; Newbold, C; Berriman, M",Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts,NATURE COMMUNICATIONS,5,,,4754,10.1038/ncomms5754,"Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host-parasite interface may have mediated host switching."
5,1,1,7,6,speciation time (small tree),no spatial aspect,none - theoretical,whole genome,both,Jamie Winternitz,2014,https://doi.org/10.1186/1471-2164-15-663,"Kupczok, A; Bollback, JP",Motif depletion in bacteriophages infecting hosts with CRISPR systems,BMC GENOMICS,15,,,663,10.1186/1471-2164-15-663,"Background: CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short motifs close to the target sequence that are required for interference in CRISPR types I and II. Here, we investigate whether PAMs are depleted in phage genomes due to selection pressure to escape recognition. Results: To this end, we analyzed two data sets. Phages infecting all bacterial hosts were analyzed first, followed by a detailed analysis of phages infecting the genus Streptococcus, where PAMs are best understood. We use two different measures of motif underrepresentation that control for codon bias and the frequency of submotifs. We compare phages infecting species with a particular CRISPR type to those infecting species without that type. Since only known PAMs were investigated, the analysis is restricted to CRISPR types I-C and I-E and in Streptococcus to types I-C and II. We found evidence for PAM depletion in Streptococcus phages infecting hosts with CRISPR type I-C, in Vibrio phages infecting hosts with CRISPR type I-E and in Streptococcus thermopilus phages infecting hosts with type II-A, known as CRISPR3. Conclusions: The observed motif depletion in phages with hosts having CRISPR can be attributed to selection rather than to mutational bias, as mutational bias should affect the phages of all hosts. This observation implies that the CRISPR system has been efficient in the groups discussed here."
4,2,1,7,6,many generations,local (one population),none - theoretical,whole genome,both,Scott Edwards,2014,https://doi.org/10.1111/evo.12427,"Tellier, A; Moreno-Gamez, S; Stephan, W",SPEED OF ADAPTATION AND GENOMIC FOOTPRINTS OF HOST-PARASITE COEVOLUTION UNDER ARMS RACE AND TRENCH WARFARE DYNAMICS,EVOLUTION,68,2211,2224,,10.1111/evo.12427,"Coevolution between hosts and their parasites is expected to follow a range of possible dynamics, the two extreme cases being called trench warfare (or Red Queen) and arms races. Long-term stable polymorphism at the host and parasite coevolving loci is characteristic of trench warfare, and is expected to promote molecular signatures of balancing selection, while the recurrent allele fixation in arms races should generate selective sweeps. We compare these two scenarios using a finite size haploid gene-for-gene model that includes both mutation and genetic drift. We first show that trench warfare do not necessarily display larger numbers of coevolutionary cycles per unit of time than arms races. We subsequently perform coalescent simulations under these dynamics to generate sequences at both host and parasite loci. Genomic footprints of recurrent selective sweeps are often found, whereas trench warfare yield signatures of balancing selection only in parasite sequences, and only in a limited parameter space. Our results suggest that deterministic models of coevolution with infinite population sizes do not predict reliably the observed genomic signatures, and it may be best to study parasite rather than host populations to find genomic signatures of coevolution, such as selective sweeps or balancing selection."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Host,Scott Edwards,2014,https://doi.org/10.1016/j.jprot.2013.12.008,"Castellanos-Martinez, S; Diz, AP; Alvarez-Chaver, P; Gestal, C",Proteomic characterization of the hemolymph of Octopus vulgaris infected by the protozoan parasite Aggregata octopiana,JOURNAL OF PROTEOMICS,105,151,163,,10.1016/j.jprot.2013.12.008,"The immune system of cephalopods is poorly known to date. The lack of genomic information makes difficult to understand vital processes like immune defense mechanisms and their interaction with pathogens at molecular level. The common octopus Octopus vulgaris has a high economic relevance and potential for aquaculture. However, disease outbreaks provoke serious reductions in production with potentially severe economic losses. In this study, a proteomic approach is used to analyze the immune response of O. vulgaris against the coccidia Aggregata octopiana, a gastrointestinal parasite which impairs the cephalopod nutritional status. The hemocytes and plasma proteomes were compared by 2-DE between sick and healthy octopus. The identities of 12 differentially expressed spots and other 27 spots without significant alteration from hemocytes, and 5 spots from plasma, were determined by mass spectrometry analysis aided by a six reading-frame translation of an octopus hemocyte RNA-seq database and also public databases. Principal component analysis pointed to 7 proteins from hemocytes as the major contributors to the overall difference between levels of infection and so could be considered as potential biomarkers. Particularly, filamin, fascin and peroxiredoxin are highlighted because of their implication in octopus immune defense activity. From the octopus plasma, hemocyanin was identified. This work represents a first step forward in order to characterize the protein profile of O. vulgaris hemolymph, providing important information for subsequent studies of the octopus immune system at molecular level and also to the understanding of the basis of octopus tolerance-resistance to A. octopiana. Biological significance The immune system of cephalopods is poorly known to date. The lack of genomic information makes difficult to understand vital processes like immune defense mechanisms and their interaction with pathogens at molecular level. The study herein presented is focused to the comprehension of the octopus immune defense against a parasite infection. Particularly, it is centered in the host parasite relationship developed between the octopus and the protozoan A. octopiana, which induces severe gastrointestinal injuries in octopus that produce a malabsorption syndrome. The common octopus is a commercially important species with a high potential for aquaculture in semi-open systems, and this pathology reduces the condition of the octopus populations on-growing in open-water systems resulting in important economical loses. This is the first proteomic approach developed on this host parasite relationship, and therefore, the contribution of this work goes from i) ecological, since this particular relationship is tending to be established as a model of host parasite interaction in natural populations; ii) evolutionary, due to the characterization of immune molecules that could contribute to understand the functioning of the immune defense in these highly evolved mollusks; and ill) to economical view. The results of this study provide an overview of the octopus hemolymph proteome. Furthermore, proteins influenced by the level of infection and implicated in the octopus cellular response are also showed. Consequently, a set of biomarkers for disease resistance is suggested for further research that could be valuable for the improvement of the octopus culture, taken into account their high economical value, the declining of landings and the need for the diversification of reared species in order to ensure the growth of the aquaculture activity. Although cephalopods are model species for biomedical studies and possess potential in aquaculture, their genomes have not been sequenced yet, which limits the application of genomic data to research important biological processes. Similarly, the octopus proteome, like other non-model organisms, is poorly represented in public databases. Most of the proteins were identified from an octopus' hemocyte RNA-seq database that we have performed, which will be the object of another manuscript in preparation. Therefore, the need to increase molecular data from non-model organisms is herein highlighted. Particularly, here is encouraged to expand the knowledge of the genomic of cephalopods in order to increase successful protein identifications. This article is part of a Special Issue entitled: Proteomics of non-model organisms. (C) 2013 Elsevier B.V. All rights reserved."
1,1,4,7,2,none,no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,Pathogen,Scott Edwards,2014,https://doi.org/10.1371/journal.pone.0098263,"Maghuly, F; Ramkat, RC; Laimer, M",Virus versus Host Plant MicroRNAs: Who Determines the Outcome of the Interaction?,PLOS ONE,9,,,e98263,10.1371/journal.pone.0098263,"Considering the importance of microRNAs (miRNAs) in the regulation of essential processes in plant pathogen interactions, it is not surprising that, while plant miRNA sequences counteract viral attack via antiviral RNA silencing, viruses in turn have developed antihost defense mechanisms blocking these RNA silencing pathways and establish a counter-defense. In the current study, computational and stem-loop Reverse Transcription - Polymerase Chain Reaction (RT-PCR) approaches were employed to a) predict and validate virus encoded mature miRNAs (miRs) in 39 DNA-A sequences of the bipartite genomes of African cassava mosaic virus (ACMV) and East African cassava mosaic virus-Uganda (EACMV-UG) isolates, b) determine whether virus encoded miRs/miRs* generated from the 5'/3' harpin arms have the capacity to bind to genomic sequences of the host plants Jatropha or cassava and c) investigate whether plant encoded miR/miR* sequences have the potential to bind to the viral genomes. Different viral pre-miRNA hairpin sequences and viral miR/miR* length variants occurring as isomiRs were predicted in both viruses. These miRNAs were located in three Open Reading Frames (ORFs) and in the Intergenic Region (IR). Moreover, various target genes for miRNAs from both viruses were predicted and annotated in the host plant genomes indicating that they are involved in biotic response, metabolic pathways and transcription factors. Plant miRs/miRs* from conserved and highly expressed families were identified, which were shown to have potential targets in the genome of both begomoviruses, representing potential plant miRNAs mediating antiviral defense. This is the first assessment of predicted viral miRs/miRs* of ACMV and EACMV-UG and host plant miRNAs, providing a reference point for miRNA identification in pathogens and their hosts. These findings will improve the understanding of host-pathogen interaction pathways and the function of viral miRNAs in Euphorbiaceous crop plants."
6,1,4,7,7,speciation time (large tree),no spatial aspect,multiple species laboratory system - no environmental aspect present,whole genome,both,Scott Edwards,2014,https://doi.org/10.1038/srep05119,"Guo, XZ; Gao, JK; Li, F; Wang, JJ",Evidence of horizontal transfer of non-autonomous Lep1 Helitrons facilitated by host-parasite interactions,SCIENTIFIC REPORTS,4,,,5119,10.1038/srep05119,"Horizontal transfer (HT) of transposable elements has been recognized to be a major force driving genomic variation and biological innovation of eukaryotic organisms. However, the mechanisms of HT in eukaryotes remain poorly appreciated. The non-autonomous Helitron family, Lep1, has been found to be widespread in lepidopteran species, and showed little interspecific sequence similarity of acquired sequences at 39 end, which makes Lep1 a good candidate for the study of HT. In this study, we describe the Lep1-like elements in multiple non-lepidopteran species, including two aphids, Acyrthosiphon pisum and Aphis gossypii, two parasitoid wasps, Cotesia vestalis, and Copidosoma floridanum, one beetle, Anoplophora glabripennis, as well as two bracoviruses in parasitoid wasps, and one intracellular microsporidia parasite, Nosema bombycis. The patchy distribution and high sequence similarity of Lep1-like elements among distantly related lineages as well as incongruence of Lep1-like elements and host phylogeny suggest the occurrence of HT. Remarkably, the acquired sequences of both NbLep1 from N . bombycis and CfLep1 from C. floridanum showed over 90% identity with their lepidopteran host Lep1. Thus, our study provides evidence of HT facilitated by host-parasite interactions. Furthermore, in the context of these data, we discuss the putative directions and vectors of HT of Lep1 Helitrons."
1,3,6,2,4,none,small spatial scale (couple of populations),single species in the wild - environment constant,full gene/regulator,Pathogen,Scott Edwards,2014,https://doi.org/10.1111/eva.12157,"Feau, N; Dutech, C; Brusini, J; Rigling, D; Robin, C",Multiple introductions and recombination in Cryphonectria hypovirus 1: perspective for a sustainable biological control of chestnut blight,EVOLUTIONARY APPLICATIONS,7,580,596,,10.1111/eva.12157,"Cryphonectria hypovirus 1 (CHV1) is a mycovirus which decreases the virulence of its fungal host Cryphonectria parasitica, the causal agent of chestnut blight recently introduced in Europe. The understanding of the evolutionary processes which have shaped CHV1 populations in Europe is required to develop a sustainable biocontrol strategy targeting chestnut blight and effective in European chestnut forests. To retrace the evolutionary history of CHV1, we analyzed sequences from two genomic regions on a collection of 55 CHV1 strains from France and northern Spain, two countries where multiple introductions of C. parasitica occurred. Several recombination events and variable selection pressures contributed to CHV1 evolution, agreeing with a non-clock-like diversification rate. These two mechanisms may be at the origin of CHV1 population diversity observed in western Europe. Considering the actual prevalence of CHV1 and its association with host genotypes, multiple introductions of CHV1 may have occurred in Europe, some of them directly from Asia and some of them through North America. Although some viral strains remained with low frequency in their introduction area, multiple infections might have allowed homologous recombination within parental sequences. Some of these recombinant lineages are associated with the spread of CHV1 in European regions."
4,2,1,7,6,many generations,local (one population),none - theoretical,whole genome,both,Scott Edwards,2014,https://doi.org/10.1603/ME13025,"Lurchachaiwong, W; Chan, TC; Richards, AL; Mccardle, W; Schuster, AL",Establishment of Orientia tsutsugamushi Lc-1 (Rickettsiales: Rickettsiaceae) Infection in ICR Outbred Mice (Rodentia: Muridae) by Needle Challenge,JOURNAL OF MEDICAL ENTOMOLOGY,51,658,660,,10.1603/ME13025,"Orientia tsutsugamushi is a pathogen transmitted by Leptotrombidium that causes scrub typhus. To develop an infection mouse model, a mite-derived isolate of O. tsutsugamushi was established from a laboratory-maintained colony of Leptotrombidium chiangraiensis (O. tsutsugamushi Lc-1). This Lc-1 isolate was initially presented to ICR (CD-1) mice by feeding an infected Lc chigger on the ear of a mouse. Once the Lc-1 was adapted to the ICR mice, quantitative real-time polymerase chain reaction was used to investigate O. tsutsugamushi genomic equivalent copies in tissues and sera. Furthermore, times to onset of the signs of infection are reported in this study. This study provides information useful for future research on this host pathogen interaction and the associated vaccine effieacy trials."
2,1,4,6,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - no environmental aspect present,exome/transcriptome,Host,Scott Edwards,2014,https://doi.org/10.4049/jimmunol.1302611,"Briolat, V; Jouneau, L; Carvalho, R; Palha, N; Langevin, C; Herbomel, P; Schwartz, O; Spaink, HP; Levraud, JP; Boudinot, P",Contrasted Innate Responses to Two Viruses in Zebrafish: Insights into the Ancestral Repertoire of Vertebrate IFN- Stimulated Genes,JOURNAL OF IMMUNOLOGY,192,4328,4341,,10.4049/jimmunol.1302611,"Ease of imaging and abundance of genetic tools make the zebrafish an attractive model host to understand host- pathogen interactions. However, basic knowledge regarding the identity of genes involved in antiviral immune responses is still lagging in this species. We conducted a microarray analysis of the larval zebrafish response to two models of RNA virus infections with very different outcomes. Chikungunya virus (CHIKV) induces a rapid and protective IFN response. Infection with infectious hematopoietic necrosis virus is lethal and is associated with a delayed and inefficient IFN response. A typical signature of IFN-stimulated genes (ISGs) was observed with both viruses, but was stronger for CHIKV. We further compared the zebrafish and human ISG repertoires and made a genomic and phylogenic characterization of the main gene families. We describe a core set of well-induced ISGs conserved across vertebrates, as well as multigenic families diversified independently in each taxon. The conservation of ISGs involved in antiviral signaling indicates conservation of the main feedback loops in these pathways. Whole-mount in situ hybridization of selected transcripts in infected larvae revealed a typical pattern of expression for ISGs in the liver, gut, and blood vessels with both viruses. We further show that some inflammatory genes were additionally induced through IFN-independent pathways by infectious hematopoietic necrosis virus and not by CHIKV. This study provides a useful reference set for the analysis of host-virus interactions in zebrafish and highlights the differences between protective and nonprotective antiviral innate responses."
3,3,6,6,6,few generations,small spatial scale (couple of populations),single species in the wild - environment constant,exome/transcriptome,Host,Scott Edwards,2014,https://doi.org/10.1186/1471-2164-15-305,"Zhang, Q; Hill, GE; Edwards, SV; Backstrom, N","A house finch (Haemorhous mexicanus) spleen transcriptome reveals intra- and interspecific patterns of gene expression, alternative splicing and genetic diversity in passerines",BMC GENOMICS,15,,,305,10.1186/1471-2164-15-305,"Background: With its plumage color dimorphism and unique history in North America, including a recent population expansion and an epizootic of Mycoplasma gallisepticum (MG), the house finch (Haemorhous mexicanus) is a model species for studying sexual selection, plumage coloration and host-parasite interactions. As part of our ongoing efforts to make available genomic resources for this species, here we report a transcriptome assembly derived from genes expressed in spleen. Results: We characterize transcriptomes from two populations with different histories of demography and disease exposure: a recently founded population in the eastern US that has been exposed to MG for over a decade and a native population from the western range that has never been exposed to MG. We utilize this resource to quantify conservation in gene expression in passerine birds over approximately 50 MY by comparing splenic expression profiles for 9,646 house finch transcripts and those from zebra finch and find that less than half of all genes expressed in spleen in either species are expressed in both species. Comparative gene annotations from several vertebrate species suggest that the house finch transcriptomes contain similar to 15 genes not yet found in previously sequenced vertebrate genomes. The house finch transcriptomes harbour similar to 85,000 SNPs, similar to 20,000 of which are non-synonymous. Although not yet validated by biological or technical replication, we identify a set of genes exhibiting differences between populations in gene expression (n = 182; 2% of all transcripts), allele frequencies (76 F-ST ouliers) and alternative splicing as well as genes with several fixed non-synonymous substitutions; this set includes genes with functions related to double-strand break repair and immune response. Conclusions: The two house finch spleen transcriptome profiles will add to the increasing data on genome and transcriptome sequence information from natural populations. Differences in splenic expression between house finch and zebra finch imply either significant evolutionary turnover of splenic expression patterns or different physiological states of the individuals examined. The transcriptome resource will enhance the potential to annotate an eventual house finch genome, and the set of gene-based high-quality SNPs will help clarify the genetic underpinnings of host-pathogen interactions and sexual selection."
1,5,2,7,6,none,global spatial scale,single species laboratory system - no environmental aspect,whole genome,Pathogen,Scott Edwards,2014,https://doi.org/10.7717/peerj.340,"Pettengill, JB; Timme, RE; Barrangou, R; Toro, M; Allard, MW; Strain, E; Musser, SM; Brown, EW",The evolutionary history and diagnostic utility of the CRISPR-Cas system within Salmonella enterica ssp enterica,PEERJ,2,,,e340,10.7717/peerj.340,"Evolutionary studies of clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (cas) genes can provide insights into host-pathogen co-evolutionary dynamics and the frequency at which different genomic events (e.g., horizontal vs. vertical transmission) occur. Within this study, we used whole genome sequence (WGS) data to determine the evolutionary history and genetic diversity of CRISPR loci and cas genes among a diverse set of 427 Salmonella enterica ssp. enterica isolates representing 64 different serovars. We also evaluated the performance of CRISPR loci for typing when compared to whole genome and multilocus sequence typing (MLST) approaches. We found that there was high diversity in array length within both CRISPR1 (median = 22; min = 3; max = 79) and CRISPR2 (median = 27; min = 2; max = 221). There was also much diversity within serovars (e.g., arrays differed by as many as 50 repeat-spacer units among Salmonella ser. Senftenberg isolates). Interestingly, we found that there are two general cas gene profiles that do not track phylogenetic relationships, which suggests that non-vertical transmission events have occurred frequently throughout the evolutionary history of the sampled isolates. There is also considerable variation among the ranges of pairwise distances estimated within each cas gene, which may be indicative of the strength of natural selection acting on those genes. We developed a novel clustering approach based on CRISPR spacer content, but found that typing based on CRISPRs was less accurate than the MLST-based alternative; typing based on WGS data was the most accurate. Notwithstanding cost and accessibility, we anticipate that draft genome sequencing, due to its greater discriminatory power, will eventually become routine for traceback investigations."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Scott Edwards,2014,https://doi.org/10.4014/jmb.1312.12082,"Park, YS; Jeong, H; Sim, YM; Yi, HS; Ryu, CM",Genome Sequence and Comparative Genome Analysis of Pseudomonas syringae pv. syringae Type Strain ATCC 19310,JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY,24,563,567,,10.4014/jmb.1312.12082,"Pseudomonas syringae pv. syringae (Psy) is a major bacterial pathogen of many economically important plant species. Despite the severity of its impact, the genome sequence of the type strain has not been reported. Here, we present the draft genome sequence of Psy ATCC 19310. Comparative genomic analysis revealed that Psy ATCC 19310 is closely related to Psy B728a. However, only a few type III effectors, which are key virulence factors, are shared by the two strains, indicating the possibility of host-pathogen specificity and genome dynamics, even under the pathovar level."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Scott Edwards,2014,https://doi.org/10.1093/nar/gku075,"Atkinson, NJ; Witteveldt, J; Evans, DJ; Simmonds, P",The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterization of the innate cellular pathways underlying virus attenuation and enhanced replication,NUCLEIC ACIDS RESEARCH,42,4527,4545,,10.1093/nar/gku075,"Most RNA viruses infecting mammals and other vertebrates show profound suppression of CpG and UpA dinucleotide frequencies. To investigate this functionally, mutants of the picornavirus, echovirus 7 (E7), were constructed with altered CpG and UpA compositions in two 1.1-1.3 Kbase regions. Those with increased frequencies of CpG and UpA showed impaired replication kinetics and higher RNA/infectivity ratios compared with wild-type virus. Remarkably, mutants with CpGs and UpAs removed showed enhanced replication, larger plaques and rapidly outcompeted wild-type virus on co-infections. Luciferase-expressing E7 sub-genomic replicons with CpGs and UpAs removed from the reporter gene showed 100-fold greater luminescence. E7 and mutants were equivalently sensitive to exogenously added interferon-beta, showed no evidence for differential recognition by ADAR1 or pattern recognition receptors RIG-I, MDA5 or PKR. However, kinase inhibitors roscovitine and C16 partially or entirely reversed the attenuated phenotype of high CpG and UpA mutants, potentially through inhibition of currently uncharacterized pattern recognition receptors that respond to RNA composition. Generating viruses with enhanced replication kinetics has applications in vaccine production and reporter gene construction. More fundamentally, the findings introduce a new evolutionary paradigm where dinucleotide composition of viral genomes is subjected to selection pressures independently of coding capacity and profoundly influences host-pathogen interactions."
2,1,2,6,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - no environmental aspect,exome/transcriptome,Pathogen,Scott Edwards,2014,https://doi.org/10.1371/journal.pone.0092239,"Gallardo-Escarate, C; Valenzuela-Munoz, V; Nunez-Acuna, G",RNA-Seq Analysis Using De Novo Transcriptome Assembly as a Reference for the Salmon Louse Caligus rogercresseyi,PLOS ONE,9,,,e92239,10.1371/journal.pone.0092239,"Despite the economic and environmental impacts that sea lice infestations have on salmon farming worldwide, genomic data generated by high-throughput transcriptome sequencing for different developmental stages, sexes, and strains of sea lice is still limited or unknown. In this study, RNA-seq analysis was performed using de novo transcriptome assembly as a reference for evidenced transcriptional changes from six developmental stages of the salmon louse Caligus rogercresseyi. EST-datasets were generated from the nauplius I, nauplius II, copepodid and chalimus stages and from female and male adults using MiSeq Illumina sequencing. A total of 151,788,682 transcripts were yielded, which were assembled into 83,444 high quality contigs and subsequently annotated into roughly 24,000 genes based on known proteins. To identify differential transcription patterns among salmon louse stages, cluster analyses were performed using normalized gene expression values. Herein, four clusters were differentially expressed between nauplius I-II and copepodid stages (604 transcripts), five clusters between copepodid and chalimus stages (2,426 transcripts), and six clusters between female and male adults (2,478 transcripts). Gene ontology analysis revealed that the nauplius I-II, copepodid and chalimus stages are mainly annotated to aminoacid transfer/repair/breakdown, metabolism, molting cycle, and nervous system development. Additionally, genes showing differential transcription in female and male adults were highly related to cytoskeletal and contractile elements, reproduction, cell development, morphogenesis, and transcription-translation processes. The data presented in this study provides the most comprehensive transcriptome resource available for C. rogercresseyi, which should be used for future genomic studies linked to host-parasite interactions."
6,1,4,3,7,speciation time (large tree),no spatial aspect,multiple species laboratory system - no environmental aspect present,gene family/microsatellites,Pathogen,Scott Edwards,2014,https://doi.org/10.1007/s00284-013-0507-2,"Deng, WY; Xiang, XH; Xie, JP",Comparative Genomic and Proteomic Anatomy of Mycobacterium Ubiquitous Esx Family Proteins: Implications in Pathogenicity and Virulence,CURRENT MICROBIOLOGY,68,558,567,,10.1007/s00284-013-0507-2,"Secreted proteins are among the most important molecules involved in host-pathogen interaction of Mycobacterium tuberculosis, the etiological agent of human tuberculosis (TB). M. tuberculosis encodes five types of VII secretion systems (ESX-1 to ESX-5) responsible for the exportation of many proteins. This system mediated substrates including members of the Esx family implicated in tuberculosis pathogenesis and survival within host cells. However, the distribution and evolution of this family remain elusive. To explore the evolution and distribution of Esx family proteins, we analyzed all available Mycobacteria genomes. Interestingly, amino mutations among M. tuberculosis esx family proteins may relate to their functions. We further analyzed the differences between pathogenic Mycobacteria, the attenuated Mycobacteria and non-pathogenic Mycobacteria. The stability, the globular domains and the phosphorylation of serine/threonine residues of M. tuberculosis esx proteins with their homologies among other Mycoabcteria were analyzed. Our comparative genomic and proteomic analysis found that the change of stability, gain or loss of globular domains and phosphorylation of serine/threonine might be responsible for the difference between the pathogenesis and virulence of the esx proteins and its homolog widespread among Mycobacteria and related species, which may provide clues for novel anti-tuberculosis drug targets."
6,1,8,1,7,speciation time (large tree),no spatial aspect,multiple species in the wild - environment constant,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Scott Edwards,2014,https://doi.org/10.1186/1471-2148-14-59,"Bellec, L; Clerissi, C; Edern, R; Foulon, E; Simon, N; Grimsley, N; Desdevises, Y",Cophylogenetic interactions between marine viruses and eukaryotic picophytoplankton,BMC EVOLUTIONARY BIOLOGY,14,,,59,10.1186/1471-2148-14-59,"Background: Numerous studies have investigated cospeciation (or cophylogeny) in various host-symbiont systems, and different patterns were inferred, from strict cospeciation where symbiont phylogeny mirrors host phylogeny, to complete absence of correspondence between trees. The degree of cospeciation is generally linked to the level of host specificity in the symbiont species and the opportunity they have to switch hosts. In this study, we investigated cophylogeny for the first time in a microalgae-virus association in the open sea, where symbionts are believed to be highly host-specific but have wide opportunities to switch hosts. We studied prasinovirus-Mamiellales associations using 51 different viral strains infecting 22 host strains, selected from the characterisation and experimental testing of the specificities of 313 virus strains on 26 host strains. Results: All virus strains were restricted to their host genus, and most were species-specific, but some of them were able to infect different host species within a genus. Phylogenetic trees were reconstructed for viruses and their hosts, and their congruence was assessed based on these trees and the specificity data using different cophylogenetic methods, a topology-based approach, Jane, and a global congruence method, ParaFit. We found significant congruence between virus and host trees, but with a putatively complex evolutionary history. Conclusions: Mechanisms other than true cospeciation, such as host-switching, might explain a part of the data. It has been observed in a previous study on the same taxa that the genomic divergence between host pairs is larger than between their viruses. It implies that if cospeciation predominates in this algae-virus system, this would support the hypothesis that prasinoviruses evolve more slowly than their microalgal hosts, whereas host switching would imply that these viruses speciated more recently than the divergence of their host genera."
1,3,7,5,4,none,small spatial scale (couple of populations),single species in the wild - environment changing,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Scott Edwards,2014,https://doi.org/10.1371/journal.pone.0091672,"Zueva, KJ; Lumme, J; Veselov, AE; Kent, MP; Lien, S; Primmer, CR",Footprints of Directional Selection in Wild Atlantic Salmon Populations: Evidence for Parasite-Driven Evolution?,PLOS ONE,9,,,e91672,10.1371/journal.pone.0091672,"Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved."
2,1,4,6,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - no environmental aspect present,exome/transcriptome,Host,Scott Edwards,2014,https://doi.org/10.1186/1471-2164-15-200,"Sutherland, BJG; Koczka, KW; Yasuike, M; Jantzen, SG; Yazawa, R; Koop, BF; Jones, SRM","Comparative transcriptomics of Atlantic Salmo salar, chum Oncorhynchus keta and pink salmon O. gorbuscha during infections with salmon lice Lepeophtheirus salmonis",BMC GENOMICS,15,,,200,10.1186/1471-2164-15-200,"Background: Salmon species vary in susceptibility to infections with the salmon louse (Lepeophtheirus salmonis). Comparing mechanisms underlying responses in susceptible and resistant species is important for estimating impacts of infections on wild salmon, selective breeding of farmed salmon, and expanding our knowledge of fish immune responses to ectoparasites. Herein we report three L. salmonis experimental infection trials of co-habited Atlantic Salmo salar, chum Oncorhynchus keta and pink salmon O. gorbuscha, profiling hematocrit, blood cortisol concentrations, and transcriptomic responses of the anterior kidney and skin to the infection. Results: In all trials, infection densities (lice per host weight (g)) were consistently highest on chum salmon, followed by Atlantic salmon, and lowest in pink salmon. At 43 days post-exposure, all lice had developed to motile stages, and infection density was uniformly low among species. Hematocrit was reduced in infected Atlantic and chum salmon, and cortisol was elevated in infected chum salmon. Systemic transcriptomic responses were profiled in all species and large differences in response functions were identified between Atlantic and Pacific (chum and pink) salmon. Pink and chum salmon up-regulated acute phase response genes, including complement and coagulation components, and down-regulated antiviral immune genes. The pink salmon response involved the largest and most diverse iron sequestration and homeostasis mechanisms. Pattern recognition receptors were up-regulated in all species but the active components were often species-specific. C-type lectin domain family 4 member M and acidic mammalian chitinase were specifically up-regulated in the resistant pink salmon. Conclusions: Experimental exposures consistently indicated increased susceptibility in chum and Atlantic salmon, and resistance in pink salmon, with differences in infection density occurring within the first three days of infection. Transcriptomic analysis suggested candidate resistance functions including local inflammation with cytokines, specific innate pattern recognition receptors, and iron homeostasis. Suppressed antiviral immunity in both susceptible and resistant species indicates the importance of future work investigating co-infections of viral pathogens and lice."
1,1,2,7,2,none,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,Pathogen,Scott Edwards,2014,https://doi.org/10.1016/j.mehy.2013.12.023,"Hande, S; Goswami, K; Jena, L; Reddy, MVR",Exploring apposite therapeutic target for apoptosis in filarial parasite: A plausible hypothesis,MEDICAL HYPOTHESES,82,356,361,,10.1016/j.mehy.2013.12.023,"Human lymphatic filariasis is a parasitic disease with profound socioeconomic encumbrance owing to its associated disability, affecting predominantly but not limited to the developing nations of tropics and subtropics. There are several technical issues like poor therapeutic and preventive repertoire as well as administrative and infrastructural limitations which jeopardize the salvage measures and further complicate the plight. Therefore, considering the gravity of the problem, WHO has mandated (under tropical disease research scheme) for placing emphasis on validation of novel therapeutic targets against this disease with the unfortunate tag of 'neglected tropical disease'. However, dearth of knowledge of parasite biology viciously coupled with difficulty of access to parasitic material from suitable animal model along with growing cost burden of high end research poses formidable challenge. Based on the recent research evidences, here we propose a premise with targeted apoptotic impact as a novel rationale to be exploited towards anti-parasitic drug development. The new era of bioinformatics ushers in new optimism with a wide range of genomic and proteomic database in public domain. Such platform might offer wonders for drug research, but needs highly selective criterion specificity. In order to test our hypothesis presumptively, we deployed a scheme for identification of target proteins from filarial parasitic origin through wide database search with precise criteria of non-homology against the host along with functional essentiality for the parasite. Further screening for proteins with growth potential from such list of essential non-homologous proteins was undertaken to mine out suitable representative target for ensuing apoptotic impact though effective inhibitors. A unique protein enzyme, RNA dependent RNA polymerase, which besides its vital role in RNA virus is believed to have regulatory role in gene expression, emerged as a plausible target. This protein is rather unknown in human host and present in related nematode parasites including the pathogen of human lymphatic parasite. Further exploitation of bioinformatics approach with a proven inhibitor of this enzyme by molecular docking technique revealed the feasibility as valid antifilarial candidate. This strategy also underscored the significance of bioinformatics tools in circumventing the resource intensive research for drug development. This virtually verified paradigm need to be tested in real lab setting not only for therapeutic authentication of this novel rationale but also for development of insight into parasitic biology that may open up new outlook in host parasite relationship. If successful, this might ensure effective measure against this menace of such 'neglected tropical parasitic diseases'. (C) 2014 Elsevier Ltd. All rights reserved."
4,1,2,7,5,many generations,no spatial aspect,single species laboratory system - no environmental aspect,whole genome,both,Scott Edwards,2014,https://doi.org/10.1111/mec.12662,"Jalasvuori, M; Lehtonen, J",Virus epidemics can lead to a population-wide spread of intragenomic parasites in a previously parasite-free asexual population,MOLECULAR ECOLOGY,23,987,991,,10.1111/mec.12662,"Sexual reproduction is problematic to explain due to its costs, most notably the twofold cost of sex. Yet, sex has been suggested to be favourable in the presence of proliferating intragenomic parasites given that sexual recombination provides a mechanism to confine the accumulation of deleterious mutations. Kraaijeveld etal. compared recently the accumulation of transposons in sexually and asexually reproducing lines of the same species, the parasitoid wasp Leptopilina clavipes. They discovered that within asexually reproducing wasps, the number of gypsy-like retrotransposons was increased fourfold, whereas other retrotransposons were not. Interestingly, gypsy-like retrotransposons are closely related to retroviruses. Endogenous retroviruses are retroviruses that have integrated to the germ line cells and are inherited thereafter vertically. They can also replicate within the genome similarly to retrotransposons as well as form virus particles and infect previously uninfected cells. This highlights the possibility that endogenous retroviruses could play a role in the evolution of sexual reproduction. Here, we show with an individual-based computational model that a virus epidemic within a previously parasite-free asexual population may establish a new intragenomic parasite to the population. Moreover and in contrast to other transposons, the possibility of endogenous viruses to maintain a virus epidemic and simultaneously provide resistance to individuals carrying active endogenous viruses selects for the presence of active intragenomic parasites in the population despite their deleterious effects. Our results suggest that the viral nature of certain intragenomic parasites should be taken into account when sex and its benefits are being considered."
1,1,3,7,2,none,no spatial aspect,single species laboratory system - environmental aspect present,whole genome,Pathogen,Kathrin Naepflin,2014,https://doi.org/10.1128/mBio.00969-14,"Becavin, C; Bouchier, C; Lechat, P; Archambaud, C; Creno, S; Gouin, E; Wu, ZF; Kuhbacher, A; Brisse, S; Pucciarelli, MG; Garcia-del Portillo, F; Hain, T; Portnoy, DA; Chakraborty, T; Lecuit, M; Pizarro-Cerda, J; Moszer, I; Bierne, H; Cossart, P","Comparison of Widely Used Listeria monocytogenes Strains EGD, 10403S, and EGD-e Highlights Genomic Differences Underlying Variations in Pathogenicity",MBIO,5,,,e00969-14,10.1128/mBio.00969-14,"For nearly 3 decades, listeriologists and immunologists have used mainly three strains of the same serovar (1/2a) to analyze the virulence of the bacterial pathogen Listeria monocytogenes. The genomes of two of these strains, EGD-e and 10403S, were released in 2001 and 2008, respectively. Here we report the genome sequence of the third reference strain, EGD, and extensive genomic and phenotypic comparisons of the three strains. Strikingly, EGD-e is genetically highly distinct from EGD (29,016 single nucleotide polymorphisms [SNPs]) and 10403S (30,296 SNPs), and is more related to serovar 1/2c than 1/2a strains. We also found that while EGD and 10403S strains are genetically very close (317 SNPs), EGD has a point mutation in the transcriptional regulator PrfA (PrfA*), leading to constitutive expression of several major virulence genes. We generated an EGD-e PrfA* mutant and showed that EGD behaves like this strain in vitro, with slower growth in broth and higher invasiveness in human cells than those of EGD-e and 10403S. In contrast, bacterial counts in blood, liver, and spleen during infection in mice revealed that EGD and 10403S are less virulent than EGD-e, which is itself less virulent than EGD-e PrfA*. Thus, constitutive expression of PrfA-regulated virulence genes does not appear to provide a significant advantage to the EGD strain during infection in vivo, highlighting the fact that in vitro invasion assays are not sufficient for evaluating the pathogenic potential of L. monocytogenes strains. Together, our results pave the way for deciphering unexplained differences or discrepancies in experiments using different L. monocytogenes strains. IMPORTANCE Over the past 3 decades, Listeria has become a model organism for host-pathogen interactions, leading to critical discoveries in a broad range of fields, including bacterial gene regulation, cell biology, and bacterial pathophysiology. Scientists studying Listeria use primarily three pathogenic strains: EGD, EGD-e, and 10403S. Despite many studies on EGD, it is the only one of the three strains whose genome has not been sequenced. Here we report the sequence of its genome and a series of important genomic and phenotypic differences between the three strains, in particular, a critical mutation in EGD's PrfA, the main regulator of Listeria virulence. Our results show that the three strains display differences which may play an important role in the virulence differences observed between the strains. Our findings will be of critical relevance to listeriologists and immunologists who have used or may use Listeria as a tool to study the pathophysiology of listeriosis and immune responses."
1,1,2,2,2,none,no spatial aspect,single species laboratory system - no environmental aspect,full gene/regulator,Pathogen,Kathrin Naepflin,2014,https://doi.org/10.1128/JB.01073-13,"Chen, A; Seifert, HS",Saturating Mutagenesis of an Essential Gene: a Majority of the Neisseria gonorrhoeae Major Outer Membrane Porin (PorB) Is Mutable,JOURNAL OF BACTERIOLOGY,196,540,547,,10.1128/JB.01073-13,"The major outer membrane porin (PorB) of Neisseria gonorrhoeae is an essential protein that mediates ion exchange between the organism and its environment and also plays multiple roles in human host pathogenesis. To facilitate structure-function studies of porin's multiple roles, we performed saturating mutagenesis at the porB locus and used deep sequencing to identify essential versus mutable residues. Random mutations in porB were generated in a plasmid vector, and mutant gene pools were transformed into N. gonorrhoeae to select for alleles that maintained bacterial viability. Deep sequencing of the input plasmid pools and the output N. gonorrhoeae genomic DNA pools identified mutations present in each, and the mutations in both pools were compared to determine which changes could be tolerated by the organism. We examined the mutability of 328 amino acids in the mature PorB protein and found that 308 of them were likely to be mutable and that 20 amino acids were likely to be non-mutable. A subset of these predictions was validated experimentally. This approach to identifying essential amino acids in a protein of interest introduces an additional application for next-generation sequencing technology and provides a template for future studies of both porin and other essential bacterial genes."
1,1,3,1,2,none,no spatial aspect,single species laboratory system - environmental aspect present,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Kathrin Naepflin,2014,https://doi.org/10.4014/jmb.1308.08092,"Hu, YQ; Huang, JL; Jiao, XA",Screening of Genes Expressed In Vivo During Interaction Between Chicken and Campylobacter jejuni,JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY,24,217,224,,10.4014/jmb.1308.08092,"Chicken are considered as the most important source of human infection by Campylobacter jejuni, which primarily arises from contaminated poultry meats. However, the genes expressed in vivo of the interaction between chicken and C. jejuni have not been screened. In this regard, in vivo-induced antigen technology (IVIAT) was applied to identify expressed genes in vivo during interaction between chicken and C. jejuni, a prevalent foodborne pathogen worldwide. Chicken sera were obtained by inoculating C. jejuni NCTC 11168 into Leghorn chickens through oral and intramuscular administration. Pooled chicken sera, adsorbed against in vitro-grown cultures of C. jejuni, were used to screen the inducible expression library of genomic proteins from sequenced C. jejuni NCTC 11168. Finally, 28 unique genes expressed in vivo were successfully identified after secondary and tertiary screenings with IVIAT. The genes were implicated in metabolism, molecular biosynthesis, genetic information processing, transport, regulation and other processes, in addition to Cj0092, with unknown function. Several potential virulence-associated genes were found to be expressed in vivo, including chuA, flgS, cheA, rplA, and Cj0190c. We selected four genes with different functions to compare their expression levels in vivo and in vitro using real-time RT-PCR. The results indicated that these selected genes were significantly upregulated in vivo but not in vitro. In short, the expressed genes in vivo may act as potential virulence-associated genes, the protein encoded by which may be meaningful vaccine candidate antigens for campylobacteriosis. IVIAT provides an important and efficient strategy for understanding the interaction mechanisms between Campylobacter and hosts."
2,1,5,1,3,within an individuals lifespan (single generation),no spatial aspect,multiple species laboratory system - environmental aspect present,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",both,Kathrin Naepflin,2014,https://doi.org/10.3791/50971,"Du, J; Rietman, H; Vleeshouwers, VGAA",Agroinfiltration and PVX Agroinfection in Potato and Nicotiana benthamiana,JOVE-JOURNAL OF VISUALIZED EXPERIMENTS,NA,,,e50971,10.3791/50971,"Agroinfiltration and PVX agroinfection are two efficient transient expression assays for functional analysis of candidate genes in plants. The most commonly used agent for agroinfiltration is Agrobacterium tumefaciens, a pathogen of many dicot plant species. This implies that agroinfiltration can be applied to many plant species. Here, we present our protocols and expected results when applying these methods to the potato (Solanum tuberosum), its related wild tuber-bearing Solanum species (Solanum section Petota) and the model plant Nicotiana benthamiana. In addition to functional analysis of single genes, such as resistance (R) or avirulence (Avr) genes, the agroinfiltration assay is very suitable for recapitulating the R-AVR interactions associated with specific host pathogen interactions by simply delivering R and Avr transgenes into the same cell. However, some plant genotypes can raise nonspecific defense responses to Agrobacterium, as we observed for example for several potato genotypes. Compared to agroinfiltration, detection of AVR activity with PVX agroinfection is more sensitive, more high-throughput in functional screens and less sensitive to nonspecific defense responses to Agrobacterium. However, nonspecific defense to PVX can occur and there is a risk to miss responses due to virus-induced extreme resistance. Despite such limitations, in our experience, agroinfiltration and PVX agroinfection are both suitable and complementary assays that can be used simultaneously to confirm each other's results."
2,1,3,5,3,within an individuals lifespan (single generation),no spatial aspect,single species laboratory system - environmental aspect present,"reduced representation of genome (RAD-seq, GBS, Seq capture)",Host,Kathrin Naepflin,2014,https://doi.org/10.1016/j.fob.2014.04.005,"Lui, YLE; Tan, TL; Timms, P; Hafner, LM; Tan, KH; Tan, EL",Elucidating the host-pathogen interaction between human colorectal cells and invading Enterovirus 71 using transcriptomics profiling,FEBS OPEN BIO,4,426,431,,10.1016/j.fob.2014.04.005,"Enterovirus 71 (EV71) is one of the main etiological agents for Hand, Foot and Mouth Disease (HFMD) and has been shown to be associated with severe clinical manifestation. Currently, there is no antiviral therapeutic for the treatment of HFMD patients owing to a lack of understanding of EV71 pathogenesis. This study seeks to elucidate the transcriptomic changes that result from EV71 infection. Human whole genome microarray was employed to monitor changes in genomic profiles between infected and uninfected cells. The results reveal altered expression of human genes involved in critical pathways including the immune response and the stress response. Together, data from this study provide valuable insights into the host-pathogen interaction between human colorectal cells and EV71. (C) 2014 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies."
1,1,1,1,2,none,no spatial aspect,none - theoretical,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Kathrin Naepflin,2014,https://doi.org/10.4238/2014.July.29.8,"Song, BK; Pan, MZ; Lau, YL; Wan, KL",Sequence analysis of the PIP5K locus in Eimeria maxima provides further evidence for eimerian genome plasticity and segmental organization,GENETICS AND MOLECULAR RESEARCH,13,5803,5814,,10.4238/2014.July.29.8,"Commercial flocks infected by Eimeria species parasites, including Eimeria maxima, have an increased risk of developing clinical or subclinical coccidiosis; an intestinal enteritis associated with increased mortality rates in poultry. Currently, infection control is largely based on chemotherapy or live vaccines; however, drug resistance is common and vaccines are relatively expensive. The development of new cost-effective intervention measures will benefit from unraveling the complex genetic mechanisms that underlie host-parasite interactions, including the identification and characterization of genes encoding proteins such as phosphatidylinositol 4-phosphate 5-kinase (PIP5K). We previously identified a PIP5K coding sequence within the E. maxima genome. In this study, we analyzed two bacterial artificial chromosome clones presenting a similar to 145-kb E. maxima (Weybridge strain) genomic region spanning the PIP5K gene locus. Sequence analysis revealed that similar to 95% of the simple sequence repeats detected were located within regions comparable to the previously described feature-rich segments of the Eimeria tenella genome. Comparative sequence analysis with the orthologous E. maxima (Houghton strain) region revealed a moderate level of conserved synteny. Unique segmental organizations and telomere-like repeats were also observed in both genomes. A number of incomplete transposable elements were detected and further scrutiny of these elements in both orthologous segments revealed interesting nesting events, which may play a role in facilitating genome plasticity in E. maxima. The current analysis provides more detailed information about the genome organization of E. maxima and may help to reveal genotypic differences that are important for expression of traits related to pathogenicity and virulence."
5,1,8,7,6,speciation time (small tree),no spatial aspect,multiple species in the wild - environment constant,whole genome,Pathogen,Kathrin Naepflin,2014,https://doi.org/10.1093/nar/gku322,"Jackson, AP; Otto, TD; Darby, A; Ramaprasad, A; Xia, D; Echaide, IE; Farber, M; Gahlot, S; Gamble, J; Gupta, D; Gupta, Y; Jackson, L; Malandrin, L; Malas, TB; Moussa, E; Nair, M; Reid, AJ; Sanders, M; Sharma, J; Tracey, A; Quail, MA; Weir, W; Wastling, JM; Hall, N; Willadsen, P; Lingelbach, K; Shiels, B; Tait, A; Berriman, M; Allred, DR; Pain, A",The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction,NUCLEIC ACIDS RESEARCH,42,7113,7131,,10.1093/nar/gku322,"Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5' ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct."
6,1,8,7,7,speciation time (large tree),no spatial aspect,multiple species in the wild - environment constant,whole genome,Pathogen,Kathrin Naepflin,2014,https://doi.org/10.1093/gbe/evu078,"Hahn, C; Fromm, B; Bachmann, L",Comparative Genomics of Flatworms (Platyhelminthes) Reveals Shared Genomic Features of Ecto- and Endoparastic Neodermata,GENOME BIOLOGY AND EVOLUTION,6,1105,1117,,10.1093/gbe/evu078,"The ectoparasitic Monogenea comprise a major part of the obligate parasitic flatworm diversity. Although genomic adaptations to parasitism have been studied in the endoparasitic tapeworms (Cestoda) and flukes (Trematoda), no representative of the Monogenea has been investigated yet. We present the high-quality draft genome of Gyrodactylus salaris, an economically important monogenean ectoparasite of wild Atlantic salmon (Salmo salar). A total of 15,488 gene models were identified, of which 7,102 were functionally annotated. The controversial phylogenetic relationships within the obligate parasitic Neodermata were resolved in a phylogenomic analysis using 1,719 gene models (alignment length of > 500,000 amino acids) for a set of 16 metazoan taxa. The Monogenea were found basal to the Cestoda and Trematoda, which implies ectoparasitism being plesiomorphic within the Neodermata and strongly supports a common origin of complex life cycles. Comparative analysis of seven parasitic flatworm genomes identified shared genomic features for the ecto- and endoparasitic lineages, such as a substantial reduction of the core bilaterian gene complement, including the homeodomain-containing genes, and a loss of the piwi and vasa genes, which are considered essential for animal development. Furthermore, the shared loss of functional fatty acid biosynthesis pathways and the absence of peroxisomes, the latter organelles presumed ubiquitous in eukaryotes except for parasitic protozoans, were inferred. The draft genome of G. salaris opens for future in-depth analyses of pathogenicity and host specificity of poorly characterized G. salaris strains, and will enhance studies addressing the genomics of host-parasite interactions and speciation in the highly diverse monogenean flatworms."
5,3,6,7,8,speciation time (small tree),small spatial scale (couple of populations),single species in the wild - environment constant,whole genome,Pathogen,Kathrin Naepflin,2014,https://doi.org/10.1093/gbe/evu054,"Santpere, G; Darre, F; Blanco, S; Alcami, A; Villoslada, P; Alba, MM; Navarro, A",Genome-Wide Analysis of Wild-Type Epstein-Barr Virus Genomes Derived from Healthy Individuals of the 1000 Genomes Project,GENOME BIOLOGY AND EVOLUTION,6,846,860,,10.1093/gbe/evu054,"Most people in the world (similar to 90%) are infected by the Epstein-Barr virus (EBV), which establishes itself permanently in B cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis, and different types of cancer. So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases. To perform a detailed comparative genomic analysis of EBV including, for the first time, EBV strains derived from healthy individuals, we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project. As strain B95-8 was used to transform B cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains. After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV. By mapping the natural EBV reads into the EBV reference genome (NC007605), we constructed nearly complete wild-type viral genomes from three individuals. Adding them to the five disease-derived EBV genomic sequences available in the literature, we performed an in-depth comparative genomic analysis. We found that latency genes harbor more nucleotide diversity than lytic genes and that six out of nine latency-related genes, as well as other genes involved in viral attachment and entry into host cells, packaging, and the capsid, present the molecular signature of accelerated protein evolution rates, suggesting rapid host-parasite coevolution."
1,3,6,1,4,none,small spatial scale (couple of populations),single species in the wild - environment constant,"gene/sequence fragment (e.g. part of CYTB, COI, MHC, 16S)",Pathogen,Kathrin Naepflin,2014,https://doi.org/,"Riaz, S; Lund, K; Lin, H; Walker, MA",Development and characterization of a large set of microsatellite markers for grape phylloxera (Daktulosphaira vitifoliae Fitch),VITIS,53,95,101,,,"This study describes novel simple sequence repeat (SSR) primers from a genomic DNA sequence of the grape phylloxera. A total of 130 SSR primers were designed from 145 unique sequences with di, tri, tetra and penta simple sequence repeats. The SSR primers were tested on DNA from 10 grape phylloxera strains chosen for their behavioral and geographic diversity. Eighty-nine primers generated easy to score alleles with standardized conditions of amplification. Twenty-eight new and four previously published markers were selected to genotype 32 root and leaf phylloxera samples in order to identify reliable markers for future genetic diversity and phylloxera population studies. SSR data from these samples was also used to determine the frequency of null alleles, and locus specific estimates of population differentiation and clustering. Up to six alleles were detected with a mean expected heterozygosity (He) of 0.51. The observed heterozygosity (Ho) was 0.73 and the majority of markers had higher Ho values. Null alleles for four markers were considered to be the result of homozygous genotypes. The 89 SSR loci developed in this study represent a new and informative set of markers that are easy to combine for multi-loading and suitable for large-scale genetic analyses of population structure, genetic diversity, and the origin of host specific strains in grape phylloxera."
1,1,2,2,2,none,no spatial aspect,single species laboratory system - no environmental aspect,full gene/regulator,Pathogen,Kathrin Naepflin,2014,https://doi.org/10.1371/journal.ppat.1003854,"Ukaegbu, UE; Kishore, SP; Kwiatkowski, DL; Pandarinath, C; Dahan-Pasternak, N; Dzikowski, R; Deitsch, KW",Recruitment of PfSET2 by RNA Polymerase II to Variant Antigen Encoding Loci Contributes to Antigenic Variation in P. falciparum,PLOS PATHOGENS,10,,,e1003854,10.1371/journal.ppat.1003854,"Histone modifications are important regulators of gene expression in all eukaryotes. In Plasmodium falciparum, these epigenetic marks regulate expression of genes involved in several aspects of host-parasite interactions, including antigenic variation. While the identities and genomic positions of many histone modifications have now been cataloged, how they are targeted to defined genomic regions remains poorly understood. For example, how variant antigen encoding loci (var) are targeted for deposition of unique histone marks is a mystery that continues to perplex the field. Here we describe the recruitment of an ortholog of the histone modifier SET2 to var genes through direct interactions with the C-terminal domain (CTD) of RNA polymerase II. In higher eukaryotes, SET2 is a histone methyltransferase recruited by RNA pol II during mRNA transcription; however, the ortholog in P. falciparum (PfSET2) has an atypical architecture and its role in regulating transcription is unknown. Here we show that PfSET2 binds to the unphosphorylated form of the CTD, a property inconsistent with its recruitment during mRNA synthesis. Further, we show that H3K36me3, the epigenetic mark deposited by PfSET2, is enriched at both active and silent var gene loci, providing additional evidence that its recruitment is not associated with mRNA production. Over-expression of a dominant negative form of PfSET2 designed to disrupt binding to RNA pol II induced rapid var gene expression switching, confirming both the importance of PfSET2 in var gene regulation and a role for RNA pol II in its recruitment. RNA pol II is known to transcribe non-coding RNAs from both active and silent var genes, providing a possible mechanism by which it could recruit PfSET2 to var loci. This work unifies previous reports of histone modifications, the production of ncRNAs, and the promoter activity of var introns into a mechanism that contributes to antigenic variation by malaria parasites. Author Summary Chemical modifications to histones, the proteins that serve as the primary units of chromatin, often determine whether specific genes are actively transcribed or condensed into transcriptionally silent regions of the genome. In the malaria parasite Plasmodium falciparum, histone modifications have been shown to play a significant role in controlling gene expression involved in many aspects of their lifecycle, including the complex gene expression patterns associated with antigenic variation. The various histone modifications that are found within the parasite's genome have now been extensively cataloged, and the enzymes that are responsible for adding and removing them have been identified. However, how these enzymes are recruited to specific regions of the genome to coordinate gene expression is not understood. In this paper, we provide the first evidence for recruitment of a unique histone methyltransferase to specific regions of the genome through its tethering to RNA polymerase II. We find that disruption of this interaction results in major changes in expression patterns of genes involved in antigenic variation, demonstrating the importance of regulated recruitment of histone modifiers for parasite biology."
3,1,3,3,4,few generations,no spatial aspect,single species laboratory system - environmental aspect present,gene family/microsatellites,Host,Kathrin Naepflin,2014,https://doi.org/10.1038/hortres.2014.66,"Hayes, RJ; Trent, MA; Truco, MJ; Antonise, R; Michelmore, RW; Bull, CT",The inheritance of resistance to bacterial leaf spot of lettuce caused by Xanthomonas campestris pv. vitians in three lettuce cultivars,HORTICULTURE RESEARCH,1,,,14066,10.1038/hortres.2014.66,"Lettuce yields can be reduced by the disease bacterial leaf spot (BLS) caused by the pathogen Xanthomonas campestris pv. vitians (Xcv) and host resistance is the most feasible method to reduce disease losses. The cultivars La Brillante, Pavane and Little Gem express an incompatible host-pathogen interaction as a hypersensitive response (HR) to California strains of Xcv resulting in resistance. Little was known about the inheritance of resistance; however, resistance to other lettuce pathogens is often determined by resistance gene candidates (RGCs) encoding nucleotide-binding leucine-rich repeat (NB-LRR) proteins. Therefore, we determined the inheritance of BLS resistance in the cultivars La Brillante, Little Gem and Pavane and mapped it relative to RGCs. The reaction to Xcv was analyzed in nine F-1, F-2 and recombinant inbred line populations of lettuce from HR x compatible or HR x HR crosses. The HR in La Brillante, Pavane and Little Gem is conditioned by single dominant genes, which are either allelic or closely linked genes. The resistance gene in La Brillante was designated Xanthomonas resistance 1 (Xar1) and mapped to lettuce linkage group 2. Xar1 is present in a genomic region that contains numerous NB-LRR encoding RGCs and functional pathogen resistance loci in the RGC2 family. The Xar1 gene confers a high level of BLS resistance in the greenhouse and field that can be introgressed into commercial lettuce cultivars to reduce BLS losses using molecular markers."