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Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events

Bentley, Kirsten, Alnaji, Fadi Ghassan, Woodford, Luke, Jones, Sian, Woodman, Andrew and Evans, David J. 2021. Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events. PLoS Pathogens 17 (8) , e1009676. 10.1371/journal.ppat.1009676

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Recombination is a common feature of many positive-strand RNA viruses, playing an important role in virus evolution. However, to date, there is limited understanding of the mechanisms behind the process. Utilising in vitro assays, we have previously shown that the template-switching event of recombination is a random and ubiquitous process that often leads to recombinant viruses with imprecise genomes containing sequence duplications. Subsequently, a process termed resolution, that has yet to be mechanistically studied, removes these duplicated sequences resulting in a virus population of wild type length genomes. Using defined imprecise recombinant viruses together with Oxford Nanopore and Illumina high throughput next generation sequencing technologies we have investigated the process of resolution. We show that genome resolution involves subsequent rounds of template-switching recombination with viral fitness resulting in the survival of a small subset of recombinant genomes. This alters our previously held understanding that recombination and resolution are independent steps of the process, and instead demonstrates that viruses undergo frequent and continuous recombination events over a prolonged period until the fittest viruses, predominantly those with wild type length genomes, dominate the population.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an open access article distributed under the terms of the Creative Commons Attribution License
Publisher: Public Library of Science
ISSN: 1553-7366
Date of First Compliant Deposit: 13 April 2022
Date of Acceptance: 8 August 2021
Last Modified: 13 Apr 2022 09:15

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