Ancient evolution of hepadnaviral paleoviruses and their impact on host genomes

Lytras, S., Arriagada, G. and Gifford, R. J. (2021) Ancient evolution of hepadnaviral paleoviruses and their impact on host genomes. Virus Evolution, 7(1), veab012. (doi: 10.1093/ve/veab012) (PMID:33747544) (PMCID:PMC7955980)

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Hepadnaviruses (family Hepadnaviviridae) are reverse-transcribing animal viruses that infect vertebrates. DNA sequences derived from ancient hepadnaviruses have been identified in the germline genome of numerous vertebrate species, and these ‘endogenous hepatitis B viruses’ (eHBVs) reveal aspects of the long-term coevolutionary relationship between hepadnaviruses and their vertebrate hosts. Here, we use a novel, data-oriented approach to recover and analyse the complete repertoire of eHBV elements in published animal genomes. We show that germline incorporation of hepadnaviruses is exclusive to a single vertebrate group (Sauria) and that the eHBVs contained in saurian genomes represent a far greater diversity of hepadnaviruses than previously recognised. Through in-depth characterisation of eHBV elements we establish the existence of four distinct subgroups within the genus Avihepadnavirus and trace their evolution through the Cenozoic Era. Furthermore, we provide a completely new perspective on hepadnavirus evolution by showing that the metahepadnaviruses (genus Metahepadnavirus) originated >300 million years ago in the Paleozoic Era and have historically infected a broad range of vertebrates. We also show that eHBVs have been intra-genomically amplified in some saurian lineages, and that eHBVs located at approximately equivalent genomic loci have been acquired in entirely distinct germline integration events. These findings indicate that selective forces have favoured the accumulation of hepadnaviral sequences at specific loci in the saurian germline. Our investigation provides a range of new insights into the long-term evolutionary history of reverse-transcribing DNA viruses and shows that germline incorporation of hepadnaviruses has played a role in shaping the evolution of saurian genomes.

Item Type:Articles
Additional Information:RJG and SL were funded by the Medical Research Council of the United Kingdom (MC_UU_12014/12). GA is funded by ANID/FONDECYT1180705 and ANID/FONDAP/15200002. The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data, or in writing the manuscript.
Glasgow Author(s) Enlighten ID:Gifford, Dr Robert and Lytras, Spyros
Authors: Lytras, S., Arriagada, G., and Gifford, R. J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Virus Evolution
Publisher:Oxford University Press
ISSN (Online):2057-1577
Published Online:03 March 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Virus Evolution 7(1):veab012
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
Viral Genomics and BioinformaticsAndrew DavisonMedical Research Council (MRC)MC_UU_12014/12III-MRC-GU Centre for Virus Research