The evolution, distribution and diversity of endogenous circoviral elements in vertebrate genomes

Circoviruses (family Circoviridae) are small, non-enveloped viruses that have short, single-stranded DNA genomes. Circovirus sequences are frequently recovered in metagenomic investigations, indicating that these viruses are widespread, yet they remain relatively poorly understood. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in vertebrate genomes. CVe are a useful source of information about the biology and evolution of circoviruses. In this study, we screened 362 vertebrate genome assemblies in silico to generate a catalog of CVe loci. We identified a total of 179 CVe sequences, most of which have not been reported previously. We show that these CVe loci reflect at least 19 distinct germline integration events. We determine the structure of CVe loci, identifying some that show evidence of potential functionalization. We also identify orthologous copies of CVe in snakes, fish, birds, and mammals, allowing us to add new calibrations to the timeline of circovirus evolution. Finally, we observed that some ancient CVe group robustly with contemporary circoviruses in phylogenies, with all sequences within these groups being derived from the same host class or order, implying a hitherto underappreciated stability in circovirus-host relationships. The openly available dataset constructed in this investigation provides new insights into circovirus evolution, and can be used to facilitate further studies of circoviruses and CVe

Mining genome data for endogenous viral elements and interferon stimulated genes: insights into host virus co-evolution

Paleovirology is the study of viruses over evolutionary timescales. Contemporary paleovirological analyses often rely on sequence data, derived from organism genome assemblies. These sequences are the germline inherited remnants of past viral infection, in the form of endogenous viral elements and the host immune genes that are evolving to combat viruses. Their study has found that viruses have exerted profound influences on host evolution, and highlighted the conflicts between viruses and host immunity. As genome sequencing technology cheapens, the accumulation of genome data increases, furthering the potential for paleovirological insights. However, data on ERVs, EVEs and antiviral gene evolution, are often not captured by automated annotation pipelines. As such, there is scope for investigations and tools that investigate the burgeoning bulk of genome data for virus and and antiviral gene sequence data in the search of paleovirological insight

A literature search tool for intelligent extraction of disease-associated genes

Objective: To extract disorder-associated genes from the scientific literature in PubMed with greater sensitivity for literature-based support than existing methods. Methods: We developed a PubMed query to retrieve disorder-related, original research articles. Then we applied a rule-based text-mining algorithm with keyword matching to extract target disorders, genes with significant results, and the type of study described by the article. Results: We compared our resulting candidate disorder genes and supporting references with existing databases. We demonstrated that our candidate gene set covers nearly all genes in manually curated databases, and that the references supporting the disorder–gene link are more extensive and accurate than other general purpose gene-to-disorder association databases. Conclusions: We implemented a novel publication search tool to find target articles, specifically focused on links between disorders and genotypes. Through comparison against gold-standard manually updated gene–disorder databases and comparison with automated databases of similar functionality we show that our tool can search through the entirety of PubMed to extract the main gene findings for human diseases rapidly and accurately

Diffractive optical elements for generating arbitrary line foci

The key optical component in the architecture of the linearly variable magnification telescope presented here is a conical lens. This architecture has application to Doppler radar processing and to wavelet processing. Unfortunately, the unique surface profile of a conical lens does not allow traditional grinding techniques to be used for fabrication; therefore, its fabrication is considered custom. In addition to the requirement of custom fabrication, a refractive conical lens introduces phase aberrations that are intrinsic to its conic shape. Further, due to the large prismatic component of the lens, the variable magnification telescope architecture is off-axis. To overcome the fabrication and application difficulties of a refractive lens, we consider the construction of a hybrid diffractive-refractive lens

Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses

The host innate immune response mediated by type I interferon (IFN) and the resulting up-regulation of hundreds of interferon-stimulated genes (ISGs) provide an immediate barrier to virus infection. Studies of the type I ‘interferome’ have mainly been carried out at a single species level, often lacking the power necessary to understand key evolutionary features of this pathway. Here, using a single experimental platform, we determined the properties of the interferomes of multiple vertebrate species and developed a webserver to mine the dataset. This approach revealed a conserved ‘core’ of 62 ISGs, including genes not previously associated with IFN, underscoring the ancestral functions associated with this antiviral host response. We show that gene expansion contributes to the evolution of the IFN system and that interferomes are shaped by lineage-specific pressures. Consequently, each mammal possesses a unique repertoire of ISGs, including genes common to all mammals and others unique to their specific species or phylogenetic lineages. An analysis of genes commonly down-regulated by IFN suggests that epigenetic regulation of transcription is a fundamental aspect of the IFN response. Our study provides a resource for the scientific community highlighting key paradigms of the type I IFN response

Autworks: a Cross-Disease Network Biology Application for Autism and Related Disorders

Background: The genetic etiology of autism is heterogeneous. Multiple disorders share genotypic and phenotypic traits with autism. Network based cross-disorder analysis can aid in the understanding and characterization of the molecular pathology of autism, but there are few tools that enable us to conduct cross-disorder analysis and to visualize the results. Description: We have designed Autworks as a web portal to bring together gene interaction and gene-disease association data on autism to enable network construction, visualization, network comparisons with numerous other related neurological conditions and disorders. Users may examine the structure of gene interactions within a set of disorder-associated genes, compare networks of disorder/disease genes with those of other disorders/diseases, and upload their own sets for comparative analysis. Conclusions: Autworks is a web application that provides an easy-to-use resource for researchers of varied backgrounds to analyze the autism gene network structure within and between disorders

Insights into circovirus host range from the genomic fossil record

A diverse range of DNA sequences derived from circoviruses (family Circoviridae) have been identified in samples obtained from humans and domestic animals, often in association with pathological conditions. In the majority of cases, however, little is known about the natural biology of the viruses from which these sequences are derived. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in animal genomes and provide a useful source of information about circovirus-host relationships. In this study we screened genome assemblies of 675 animal species and identified numerous circovirus-related sequences, including the first examples of CVe derived from cycloviruses. We confirmed the presence of these CVe in the germline of the elongate twig ant (Pseudomyrmex gracilis), thereby establishing that cycloviruses infect insects. We examined the evolutionary relationships between CVe and contemporary circoviruses, showing that CVe from ants and mites group relatively closely with cycloviruses in phylogenies. Furthermore, the relatively random interspersal of CVe from insect genomes with cyclovirus sequences recovered from vertebrate samples, suggested that contamination might be an important consideration in studies reporting these viruses. Our study demonstrates how endogenous viral sequences can inform metagenomics-based virus discovery. In addition, it raises doubts about the role of cycloviruses as pathogens of humans and other vertebrates

Signatures of adaptation at key insecticide resistance loci in Anopheles gambiae in Southern Ghana revealed by reduced-coverage WGS.

Resistance to insecticides and adaptation to a diverse range of environments present challenges to Anopheles gambiae s.l. mosquito control efforts in sub-Saharan Africa. Whole-genome-sequencing is often employed for identifying the genomic basis underlying adaptation in Anopheles, but remains expensive for large-scale surveys. Reduced coverage whole-genome-sequencing can identify regions of the genome involved in adaptation at a lower cost, but is currently untested in Anopheles mosquitoes. Here, we use reduced coverage WGS to investigate population genetic structure and identify signatures of local adaptation in Anopheles mosquitoes across southern Ghana. In contrast to previous analyses, we find no structuring by ecoregion, with Anopheles coluzzii and Anopheles gambiae populations largely displaying the hallmarks of large, unstructured populations. However, we find signatures of selection at insecticide resistance (IR) loci that appear ubiquitous across ecoregions in An. coluzzii, and strongest in forest ecoregions in An. gambiae. Our study highlights resistance candidate genes in this region, and validates reduced coverage WGS, potentially to very low coverage levels, for population genomics and exploratory surveys for adaptation in Anopheles taxa

Novel parvoviruses from wild and domestic animals in Brazil provide new insights into parvovirus distribution and diversity

Parvoviruses (family Parvoviridae) are small, single-stranded DNA viruses. Many parvoviral pathogens of medical, veterinary and ecological importance have been identified. In this study, we used high-throughput sequencing (HTS) to investigate the diversity of parvoviruses infecting wild and domestic animals in Brazil. We identified 21 parvovirus sequences (including twelve nearly complete genomes and nine partial genomes) in samples derived from rodents, bats, opossums, birds and cattle in Pernambuco, São Paulo, Paraná and Rio Grande do Sul states. These sequences were investigated using phylogenetic and distance-based approaches and were thereby classified into eight parvovirus species (six of which have not been described previously), representing six distinct genera in the subfamily Parvovirinae. Our findings extend the known biogeographic range of previously characterized parvovirus species and the known host range of three parvovirus genera (Dependovirus, Aveparvovirus and Tetraparvovirus). Moreover, our investigation provides a window into the ecological dynamics of parvovirus infections in vertebrates, revealing that many parvovirus genera contain well-defined sub-lineages that circulate widely throughout the world within particular taxonomic groups of hosts