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

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MacLean, Oscar A., Lytras, Spyros, Weaver, Steven, Singer, Joshua B., Boni, Maciej F., Lemey, Philippe, Kosakovsky Pond, Sergei L., Robertson, David L.·2021·PLOS Biology
DOI 10.1371/journal.pbio.3001115
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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.

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Metadata

Authors
MacLean, O. A., Lytras, S., Weaver, S., Singer, J. B., Boni, M. F., Lemey, P., Kosakovsky Pond, S. L., & Robertson, D. L.
Venue
PLOS Biology
Publisher
Public Library of Science (PLoS)
Published
2021-03-12
Volume
19
Issue
3
Pages
e3001115
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.3001115
OpenAlex
W3135415606
Cited by
200
References
20
FWCI
12.73
Type
journal article
Language
en
Update notices
new_version (2021-03-24)
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Medical Research Council (MC_UU_1201412)
  • Wellcome Trust (220977/Z/20/Z, 206369/Z/17/Z, 206298/Z/17/Z)
  • National Institutes of Health (R01 AI134384, NIH/NIAID Center of Excellence in Influenza Research and Surveillance contract (HHS N272201400007C))
  • National Science Foundation (2027196)
  • European Research Council (725422-ReservoirDOCS)
  • European Union's Horizon 2020 project MOOD (874850)
  • Research Foundation - Flanders (G066215N, G0D5117N and G0B9317N)
  • Bill and Melinda Gates Foundation (INV-005517)

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CoChat. (2026). Citation check: Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen. https://app.cochat.ai/papers/10.1371/journal.pbio.3001115
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MacLean, O. A., Lytras, S., Weaver, S., Singer, J. B., Boni, M. F., Lemey, P., Kosakovsky Pond, S. L., & 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. https://doi.org/10.1371/journal.pbio.3001115

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