Biology subjects

Wilson, S. J.

Publications and source records attributed to Wilson, S. J..

3 recordsLinked to original sources

bioRxiv2018

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.

microbiology↗

bioRxiv2018

The evolution, distribution and diversity of endogenous circoviral elements

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 can provide unique, retrospective 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.\n\nAbbreviations

evolutionary biology↗

bioRxiv2017

Evolutionary Action of de novo missense variants across pathways prioritizes genes linked to autism and predicts patient phenotypic severity

The pathogenicity of individual de novo missense mutations in autism spectrum disorder remains difficult to validate. Here we asked in 2,384 probands whether these variants exhibited collective functional impact biases across pathways. As measured with Evolutionary Action (EA) in 368 gene groupings, we found significant biases in axonogenesis, synaptic transmission, and other neurodevelopmental pathways. Strikingly, both de novo and inherited missense variants in prioritized genes correlated with patient IQ. This general integrative approach thus detects missense variants most likely to contribute to autism pathogenesis and is the first, to our knowledge, to link missense variant impact to autism phenotypic severity.

genomics↗