Biology subjects

Singer, J. B.

Publications and source records attributed to Singer, J. B..

6 recordsLinked to original sources

bioRxiv2020

Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans

RNA viruses are proficient at switching host species, and evolving adaptations to exploit the new hosts cells efficiently. Surprisingly, SARS-CoV-2 has apparently required no significant adaptation to humans since the start of the COVID-19 pandemic, with no observed selective sweeps since genome sampling began. Here we assess the types of natural selection taking place in Sarbecoviruses in horseshoe bats versus SARS-CoV-2 evolution in humans. While there is moderate evidence of diversifying positive selection in SARS-CoV-2 in humans, it is limited to the early phase of the pandemic, and purifying selection is much weaker in SARS-CoV-2 than in related bat Sarbecoviruses. In contrast, our analysis detects significant positive episodic diversifying selection acting on the bat virus lineage SARS-CoV-2 emerged from, accompanied by an adaptive depletion in CpG composition presumed to be linked to the action of antiviral mechanisms in ancestral hosts. The closest bat virus to SARS-CoV-2, RmYN02 (sharing an ancestor [~]1976), is a recombinant with a structure that includes differential CpG content in Spike; clear evidence of coinfection and evolution in bats without involvement of other species. Collectively our results demonstrate the progenitor of SARS-CoV-2 was capable of near immediate human-human transmission as a consequence of its adaptive evolutionary history in bats, not humans.

evolutionary biology↗

bioRxiv2019

Evolutionary stasis of an RNA virus indicates arbovirus re-emergence triggered by accidental release

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an insect-borne virus of ruminants, emerged in livestock in Northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of Euros. Though the outbreak was successfully controlled through vaccination by early 2010, puzzlingly a closely-related BTV-8 strain re-emerged in France in 2015, triggering a second outbreak that is still ongoing. The origin of this virus and the mechanisms underlying its re-emergence are unknown. Here, we performed phylogenetic analyses of 164 whole BTV-8 genomes sampled throughout the two outbreaks. We demonstrate consistent clock-like virus evolution during both epizootics but found negligible evolutionary change between them. We estimate that the ancestor of the second outbreak dates from the height of the first outbreak in 2008. This implies that the virus had not been replicating for multiple years prior to its re-emergence in 2015. Given the absence of any known natural mechanism that could explain BTV-8 persistence over this period without replication, we conclude that the second outbreak was most likely initiated by accidental exposure of livestock to frozen material contaminated with virus from approximately 2008. Our work highlights new targets for pathogen surveillance programmes in livestock and illustrates the power of genomic epidemiology to identify pathways of infectious disease emergence.

evolutionary biology↗

bioRxiv2018

Global genetic diversity of small ruminant lentiviruses, and a hypothesis regarding their pandemic spread.

Small ruminant lentiviruses (SRLVs) cause chronic, persistent infections in populations of domestic sheep and goats throughout the world. In this study, we use genomic data to investigate the origins and history of the SRLV pandemic. To explore the hypothesis that SRLV infection disseminated during Neolithic times, we performed a serology and DNA sequencing-based investigation of SRLVs diversity in the Fertile Crescent region, where domestication of sheep and goats is thought to have originally occurred. While we found an elevated level of viral genetic diversity compared to other regions of the world, we did not find unambiguous evidence that the Fertile Crescent region was the centre of the contemporary SRLV pandemic. We therefore examined historical reports to investigate the relationship between contemporary SRLV distribution and diversity and the emergence of SRLV-associated disease. Historical data suggested that the emergence of SRLV-associated disease might be associated with the long-distance export of exotic small ruminant breeds - in particular, karakul sheep from Central Asia - during the late 19th and early 20th centuries. Phylogeographic analysis could neither confirm nor refute this hypothesis. However, we anticipate that future accumulation of genomic data from SRLV strains found throughout the world may allow for a more definitive assessment. The openly available data and resources assembled in this study will facilitate future investigations in this area.\n\nImportanceViruses that cause chronic, persistent infections have circulated in animals for millions of years. However, many have only emerged as pathogens within the far shorter timeframe of recorded human history. It is important to understand the history of chronic viral infections in domestic animals, so that more effective control and eradication programs can be developed.

evolutionary biology↗

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

GLUE: A flexible software system for virus sequence data

Virus genome sequences, generated in ever-higher volumes, can provide new scientific insights and inform our responses to epidemics and outbreaks. To facilitate interpretation, such data must be organised and processed within scalable computing resources that encapsulate virology expertise. GLUE (Genes Linked by Underlying Evolution) is a data-centric bioinformatics environment for building such resources. Its flexible design emphasises applicability to different viruses and to diverse needs within research, clinical or public health contexts. A sequence data resource for hepatitis C virus (HCV) with clinical and research applications is presented as a case study.

bioinformatics↗

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↗