MacLean, O. A. , Lytras, S., Weaver, S., Singer, J. B., Boni, M. F., Lemey, P., Kosakovsky Pond, S. L. and Robertson, D. L. (2021) Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen. PLoS Biology, 19(3), e3001115. (doi: 10.1371/journal.pbio.3001115) (PMID:33711012) (PMCID:PMC7990310)
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Abstract
Virus host shifts are generally associated with novel adaptations to exploit the cells of the new host species optimally. Surprisingly, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has apparently required little to no significant adaptation to humans since the start of the Coronavirus Disease 2019 (COVID-19) pandemic and to October 2020. Here we assess the types of natural selection taking place in Sarbecoviruses in horseshoe bats versus the early 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 evidence for significant positive episodic diversifying selection acting at the base of 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 these ancestral bat hosts. The closest bat virus to SARS-CoV-2, RmYN02 (sharing an ancestor about 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. While an undiscovered “facilitating” intermediate species cannot be discounted, collectively, our results support the progenitor of SARS-CoV-2 being capable of efficient human–human transmission as a consequence of its adaptive evolutionary history in bats, not humans, which created a relatively generalist virus.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Robertson, Professor David and Singer, Dr Josh and Lytras, Spyros and MacLean, Dr Oscar |
Creator Roles: | MacLean, O. A.Conceptualization, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing Lytras, S.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review and editing Singer, J. B.Data curation, Resources, Software Robertson, D. L.Conceptualization, Formal analysis, Funding acquisition, Investigation, Supervision, Writing – original draft, Writing – review and editing |
Authors: | MacLean, O. A., Lytras, S., Weaver, S., Singer, J. B., Boni, M. F., Lemey, P., Kosakovsky Pond, S. L., and Robertson, D. L. |
College/School: | 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: | PLoS Biology |
Publisher: | Public Library of Science |
ISSN: | 1544-9173 |
ISSN (Online): | 1545-7885 |
Published Online: | 12 March 2021 |
Copyright Holders: | Copyright © 2021 MacLean et al. |
First Published: | First published in PLoS Biology 19(3): e3001115 |
Publisher Policy: | Reproduced under a Creative Commons License |
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