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Gifford, R. J.

Publications and source records attributed to Gifford, R. J..

9 recordsLinked to original sources

Origin and recent expansion of an endogenous gammaretroviral lineage in canids

Mammalian genomes contain a fossilized record of ancient retroviral infections in the form of endogenous retroviruses (ERVs). We used whole genome sequence data to assess the origin and evolution of the recently active ERV-Fc gammaretroviral lineage based on the record of past infections retained in the genome of the domestic dog, Canis lupus familiaris. We identified 165 loci, including 58 insertions absent from the dog reference assembly, and characterized element polymorphism across 332 canids from nine species. Insertions were found throughout the dog genome including within and near gene models. Analysis of 19 proviral sequences identified shared disruptive mutations indicating defective proviruses were spread via complementation. The patterns of ERV polymorphism and sequence variation indicate multiple circulating viruses infected canid ancestors within the last 20 million to within 1.6 million years with a recent bust of germline invasion in the lineage leading to wolves and dogs.

genomics

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

Database-integrated genome screening (DIGS): exploring genomes heuristically using sequence similarity search tools and a relational database.

A significant fraction of most genomes is comprised of DNA sequences that have been incompletely investigated. This genomic dark matter contains a wealth of useful biological information that can be recovered by systematically screening genomes in silico using sequence similarity search tools. Specialized computational tools are required to implement these screens efficiently. Here, we describe the database-integrated genome-screening (DIGS) tool: a computational framework for performing these investigations. To demonstrate, we screen mammalian genomes for endogenous viral elements (EVEs) derived from the Filoviridae, Parvoviridae, Circoviridae and Bornaviridae families, identifying numerous novel elements in addition to those that have been described previously. The DIGS tool provides a simple, robust framework for implementing a broad range of heuristic, sequence analysis-based explorations of genomic diversity.\n\nAvailabilityhttp://giffordlabcvr.github.io/DIGS-tool/\n\nContactrobert.gifford@glasgow.ac.uk\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics

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

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

Whole-genome sequencing of parvoviruses from wild and domestic animals in Brazil provides new insights into parvovirus distribution and diversity

AbstractParvoviruses (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, Sao Paulo, Parana 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.

microbiology

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

Identification of the first endogenous Ophiovirus sequence.

Endogenous viral elements (EVEs) are sequences in eukaryotic genomes that are derived from the ancestral integration of viral sequences into germline cells. Ophioviruses (family Ophioviridae) are a recently established family of viruses that infects plants. In this report, we describe the first example of an EVE derived from an ophiovirus, in the genome of eelgrass (Zostera marina). These findings extend the host range of ophioviruses to include seagrasses of the family Zosteraceae, and provide a potential time calibration for the evolution of the Ophioviridae family.

evolutionary biology

An endogenous amdoparvovirus in the genome of the Transcaucasian mole vole (Ellobius lutescens): implications for ecology and evolution of carnivore amdoparvoviruses.

Amdoparvoviruses (family Parvoviridae: genus Amdoparvovirus) infect carnivores, and are a major cause of morbidity and mortality in farmed animals. In this study, we systematically screened animal genomes to identify PVe disclosing a high degree of similarity to amdoparvoviruses, and investigated their genomic, phylogenetic and protein structural features. We report the first examples of full-length, amdoparvovirus-derived PVe in the genome of the Transcaucasian mole vole (Ellobius lutescens). Furthermore, we identify four further PVe in mammal and reptile genomes that are intermediate between amdoparvoviruses and their sister genus (Protoparvovirus) in terms of their phylogenetic placement and genomic features. In particular, we identify a genome-length PVe in the genome of a pit viper (Protobothrops mucrosquamatus) that is more like a protoparvovirus than an amdoparvovirus in terms of its phylogenetic placement and the structural features of its capsid protein (as revealed by homology modeling), yet exhibits characteristically amdoparvovirus-like genome features including: (i) a putative middle ORF gene; (ii) a capsid gene that lacks a phospholipase A2 (PLA2) domain; (iii) a genome structure consistent with an amdoparvovirus-like mechanism of capsid gene expression. Our findings indicate that amdoparvovirus host range has extended to rodents in the past, and that parvovirus lineages possessing a mixture of proto- and amdoparvovirus-like characteristics have circulated in the past. In addition, we show that PVe in the mole vole and pit viper encode intact, expressible replicase genes that have potentially been co-opted or exapted in these host species.

evolutionary biology