Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen

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)

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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
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLean, Dr Oscar and Lytras, Spyros and Robertson, Professor David and Singer, Dr Joshua
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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
Medical Research Council (MRC)MC_UU_1201412
301049Host determinants of disease outcomes in arboviral infectionsMassimo PalmariniWellcome Trust (WELLCOTR)206369/Z/17/ZIII - Centre for Virus Research