Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic.

Maciej F Boni1 Philippe Lemey2 Xiaowei Jiang3 Tommy Tsan-Yuk Lam4 Blair W Perry5 Todd A Castoe5 Andrew Rambaut6 David L Robertson7
Affiliations 7 institutions
  1. Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University, University Park, PA, USA. [email protected].
  2. Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Leuven, Belgium. [email protected].
  3. Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, China.
  4. State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
  5. Department of Biology, University of Texas Arlington, Arlington, TX, USA.
  6. Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK. [email protected].
  7. MRC-University of Glasgow Centre for Virus Research, Glasgow, UK. [email protected].

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.

Supporting text Virus Host Location
Angiotensin-Converting Enzyme 2 177 Animals 1948 Bayes Theorem 32 Betacoronavirus 78 China 229 Chiroptera 371 Coronavirus Infections 171 COVID-19 425 Evolution, Molecular 176 Genetic Variation 127 Genome, Viral 317 Humans 1440 Pandemics 108 Peptidyl-Dipeptidase A 57 Phylogeny 805 Pneumonia, Viral 42 Recombination, Genetic 59 SARS-CoV-2 453 ACE2 protein, human 87

Evidence records

3 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE3997
Key finding

The lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades, supporting bats as a long-term reservoir.

Virus
Host
Location
Not specified
Supporting text

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.

Method
Bayesian evolutionary rate and divergence date analysis
Genomic Evolution
2 records · 2 evidence types
Evidence type
1 records
OVE3994
Key finding

Sarbecoviruses undergo frequent recombination across geographically structured lineages in China.

Virus
Host
Not specified
Location
Not specified
Supporting text

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.

Event type
recombination
Evidence type
1 records
OVE3996
Key finding

Bayesian phylogenetic dating estimated that the lineage giving rise to SARS-CoV-2 diverged from bat sarbecoviruses decades ago and circulated in bats for an extended period before emergence.

Virus
Host
Location
Not specified
Supporting text

Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% 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.

Genes or proteins
68-genome sarbecovirus alignment
Analysis methods
Bayesian phylogenetic dating | evolutionary rate estimation | divergence date estimation