https://www.biorxiv.org/content/10.1101/2021.12.14.472632v1 Skip to main content bioRxiv * Home * About * Submit * ALERTS / RSS Search for this keyword [ ] [Search] Advanced Search New Results Evidence for a mouse origin of the SARS-CoV-2 Omicron variant Changshuo Wei, Ke-Jia Shan, Weiguang Wang, Shuya Zhang, Qing Huan, View ORCID ProfileWenfeng Qian doi: https://doi.org/10.1101/2021.12.14.472632 Changshuo Wei Institute of Genetics and Developmental Biology, Chinese Academy of Sciences * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Ke-Jia Shan Institute of Genetics and Developmental Biology, Chinese Academy of Sciences * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Weiguang Wang Institute of Genetics and Developmental Biology, Chinese Academy of Sciences * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Shuya Zhang Institute of Genetics and Developmental Biology, Chinese Academy of Sciences * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Qing Huan Institute of Genetics and Developmental Biology, Chinese Academy of Sciences * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Wenfeng Qian Institute of Genetics and Developmental Biology, Chinese Academy of Sciences * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Wenfeng Qian * For correspondence: wfqian@genetics.ac.cn * Abstract * Info/History * Metrics * Supplementary material * Preview PDF Loading Abstract The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting the possibility of host-jumping. The molecular spectrum (i.e., the relative frequency of the twelve types of base substitutions) of mutations acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients, but was highly consistent with spectra associated with evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak. Competing Interest Statement The authors have declared no competing interest. 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-ND 4.0 International license. View the discussion thread. Back to top PreviousNext Posted December 15, 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. Your Email * [ ] Your Name * [ ] Send To * [ ] [ ] [ ] [ ] [ ] Enter multiple addresses on separate lines or separate them with commas. 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[Send Message] Share Evidence for a mouse origin of the SARS-CoV-2 Omicron variant Changshuo Wei, Ke-Jia Shan, Weiguang Wang, Shuya Zhang, Qing Huan, Wenfeng Qian bioRxiv 2021.12.14.472632; doi: https://doi.org/10.1101/ 2021.12.14.472632 Share This Article: [https://www.biorxiv.org/content/10.1101/2021.12.14] Copy Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo Citation Tools Evidence for a mouse origin of the SARS-CoV-2 Omicron variant Changshuo Wei, Ke-Jia Shan, Weiguang Wang, Shuya Zhang, Qing Huan, Wenfeng Qian bioRxiv 2021.12.14.472632; doi: https://doi.org/10.1101/ 2021.12.14.472632 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 Areas All Articles * Animal Behavior and Cognition (3178) * Biochemistry (6492) * Bioengineering (4688) * Bioinformatics (18551) * Biophysics (8925) * Cancer Biology (6883) * Cell Biology (10023) * Clinical Trials (138) * Developmental Biology (5771) * Ecology (9066) * Epidemiology (2063) * Evolutionary Biology (12313) * Genetics (8787) * Genomics (11687) * Immunology (6679) * Microbiology (17081) * Molecular Biology (6666) * Neuroscience (37189) * Paleontology (268) * Pathology (1103) * Pharmacology and Toxicology (1895) * Physiology (2814) * Plant Biology (6180) * Scientific Communication and Education (1182) * Synthetic Biology (1724) * Systems Biology (4901) * Zoology (975)