Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Exploring the natural origins of SARS-CoV-2 in the light of recombination

View ORCID ProfileSpyros Lytras, View ORCID ProfileJoseph Hughes, Darren Martin, Arné de Klerk, Rentia Lourens, Sergei L Kosakovsky Pond, Wei Xia, View ORCID ProfileXiaowei Jiang, View ORCID ProfileDavid L Robertson
doi: https://doi.org/10.1101/2021.01.22.427830
Spyros Lytras
1MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Spyros Lytras
Joseph Hughes
1MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Joseph Hughes
Darren Martin
2Computational Biology Division, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arné de Klerk
2Computational Biology Division, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rentia Lourens
3Division of Neurosurgery, Department of Surgery, Neuroscience institute, University of Cape Town, Cape Town, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sergei L Kosakovsky Pond
4Institute for Genomics and Evolutionary Medicine, Department of Biology, Temple University, Pennsylvania, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Xia
5National School of Agricultural Institution and Development, South China Agricultural University, Guangzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaowei Jiang
6Department of Biological Sciences, Xi’an Jiaotong-Liverpool University (XJTLU), Suzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Xiaowei Jiang
David L Robertson
1MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David L Robertson
  • For correspondence: david.l.robertson@glasgow.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Summary

The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (Sarbecoviruses) have been identified, is fuelling speculation on the natural origins of SARS-CoV-2. We have comprehensively analysed phylogenetic relations between SARS-CoV-2, and the related bat and pangolin Sarbecoviruses sampled so far. Determining the likely recombination events reveals a highly reticulate evolutionary history within this group of coronaviruses. Clustering of the inferred recombination events is non-random with evidence that Spike, the main target for humoral immunity, is beside a recombination hotspot likely driving antigenic shift in the ancestry of bat Sarbecoviruses. Coupled with the geographic ranges of their hosts and the sampling locations, across southern China, and into Southeast Asia, we confirm horseshoe bats, Rhinolophus, are the likely SARS-CoV-2 progenitor reservoir species. By tracing the recombinant sequence patterns, we conclude that there has been relatively recent geographic movement and co-circulation of these viruses’ ancestors, extending across their bat host ranges in China and Southeast Asia over the last 100 years or so. We confirm that a direct proximal ancestor to SARS-CoV-2 is yet to be sampled, since the closest relative shared a common ancestor with SARS-CoV-2 approximately 40 years ago. Our analysis highlights the need for more wildlife sampling to (i) pinpoint the exact origins of SARS-CoV-2’s animal progenitor, and (ii) survey the extent of the diversity in the related Sarbecoviruses’ phylogeny that present high risk for future spillover.

Highlights

  • The origin of SARS-CoV-2 can be traced to horseshoe bats, genus Rhinolophus, with ranges in both China and Southeast Asia.

  • The closest known relatives of SARS-CoV-2 exhibit frequent transmission among their Rhinolophus host species.

  • Sarbecoviruses have undergone extensive recombination throughout their evolutionary history.

  • Accounting for the mosaic patterns of these recombinants is important when inferring relatedness to SARS-CoV-2.

  • Breakpoint patterns are consistent with recombination hotspots in the coronavirus genome, particularly upstream of the pike open reading frame with a coldspot in S1.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Our recombination analysis has been updated with additional virus genomes that had become available, and an analysis of the distribution of the identified recombination breakpoints has been included. The latter involved contributions from some additional authors.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted May 27, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Exploring the natural origins of SARS-CoV-2 in the light of recombination
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Exploring the natural origins of SARS-CoV-2 in the light of recombination
Spyros Lytras, Joseph Hughes, Darren Martin, Arné de Klerk, Rentia Lourens, Sergei L Kosakovsky Pond, Wei Xia, Xiaowei Jiang, David L Robertson
bioRxiv 2021.01.22.427830; doi: https://doi.org/10.1101/2021.01.22.427830
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Exploring the natural origins of SARS-CoV-2 in the light of recombination
Spyros Lytras, Joseph Hughes, Darren Martin, Arné de Klerk, Rentia Lourens, Sergei L Kosakovsky Pond, Wei Xia, Xiaowei Jiang, David L Robertson
bioRxiv 2021.01.22.427830; doi: https://doi.org/10.1101/2021.01.22.427830

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Evolutionary Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3602)
  • Biochemistry (7567)
  • Bioengineering (5522)
  • Bioinformatics (20782)
  • Biophysics (10325)
  • Cancer Biology (7978)
  • Cell Biology (11635)
  • Clinical Trials (138)
  • Developmental Biology (6602)
  • Ecology (10200)
  • Epidemiology (2065)
  • Evolutionary Biology (13611)
  • Genetics (9539)
  • Genomics (12844)
  • Immunology (7919)
  • Microbiology (19538)
  • Molecular Biology (7657)
  • Neuroscience (42081)
  • Paleontology (308)
  • Pathology (1257)
  • Pharmacology and Toxicology (2201)
  • Physiology (3267)
  • Plant Biology (7038)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1951)
  • Systems Biology (5426)
  • Zoology (1116)