Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic
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Abstract
There are outstanding evolutionary questions on the recent emergence of human coronavirus SARS-CoV-2 including the role of reservoir species, the role of recombination and its time of divergence from animal viruses. We find that the sarbecoviruses-the viral subgenus containing SARS-CoV and SARS-CoV-2-undergo frequent recombination and exhibit spatially structured genetic diversity on a regional scale in China. SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif, important for specificity to human ACE2 receptors, appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination. To employ phylogenetic dating methods, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were shown to be consistent for these three approaches and for two different prior specifications of evolutionary rates based on HCoV-OC43 and MERS-CoV. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 1879-1999), 1969 (95% HPD: 1930-2000) and 1982 (95% HPD: 1948-2009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades.
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SARS-CoV-2 is thought to derive from a bat SARS-CoV-related coronavirus with a furin cleavage site that increases its ability to infect human cells.
“Although the proximal origins are unknown, SARS-CoV-2 is thought to derive from a bat SARS-CoV-related coronavirus with a furin cleavage site that enhances the capacity of the virus to infect human cells.48, 49”
From The Lancet Commission on lessons for the future from the COVID-19 pandemic (2022) · cites this paper as [48]
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Large‐scale genome sampling reveals unique immunity and metabolic adaptations in bats
Moreno-Santillán, D. D., Lama, T. M., Gutiérrez‐Guerrero, Y. T., Brown, A. M., Donat, P., Zhao, H., Rossiter, S. J., Yohe, L. R., Potter, J. H. T., Teeling, E. C., et al. (2021) · Molecular Ecology · doi:10.1111/mec.16027 · Cited by 89 · see citing works
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- Authors
- Boni, M. F., Lemey, P., Jiang, X., Lam, T. T.-Y., Perry, B. W., Castoe, T. A., Rambaut, A., & Robertson, D. L.
- Affiliations
- Pennsylvania State University (US)
- KU Leuven (BE)
- Xi’an Jiaotong-Liverpool University (CN)
- University of Hong Kong (HK)
- The University of Texas at Arlington (US)
- University of Edinburgh (GB)
- MRC University of Glasgow Centre for Virus Research (GB)
- Corresponding author
- Boni, Maciej F.
- Lemey, Philippe
- Rambaut, Andrew
- Robertson, David L.
- ORCID
- Venue
- Nature Microbiology
- Published
- 2020-07-28
- Volume
- 5
- Issue
- 11
- Pages
- 1408-1417
- ISSN
- 2058-5276 (ISSN-L)
- OpenAlex
- W3046218112
- Cited by
- 1,014
- References
- 69
- Citations by year
- 2026: 23 · 2025: 46 · 2024: 79 · 2023: 118 · 2022: 240 · 2021: 327 · 2020: 178 · 2012: 1
- FWCI
- 28.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
- Lirias (KU Leuven) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Fonds Wetenschappelijk Onderzoek (G0D5117N, G0B9317N)
- Wellcome Trust (206298/Z/17/Z)
- RCUK | Medical Research Council (MC_UU_1201412)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- SARS-CoV-2, sarbecoviruses, COVID-19 pandemic, viral recombination, bat reservoirs, pangolins, divergence time estimation, receptor-binding motif, ACE2 receptor, phylogenetic dating, viral emergence, genetic diversity, SARS-CoV
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Bayes Theorem, China, Chiroptera, Humans, Peptidyl-Dipeptidase A, Phylogeny, Pneumonia, Viral, Recombination, Genetic, Genetic Variation, Genome, Viral, Coronavirus Infections, Evolution, Molecular, Pandemics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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