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Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2

View ORCID ProfileKathryn E. Kistler, View ORCID ProfileJohn Huddleston, View ORCID ProfileTrevor Bedford
doi: https://doi.org/10.1101/2021.09.11.459844
Kathryn E. Kistler
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States
2Molecular and Cellular Biology Program, University of Washington, Seattle, United States
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  • ORCID record for Kathryn E. Kistler
  • For correspondence: kistlerk@uw.edu
John Huddleston
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States
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Trevor Bedford
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States
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Abstract

Despite the appearance of variant SARS-CoV-2 viruses with altered receptorbinding or antigenic phenotypes, traditional methods for detecting adaptive evolution from sequence data do not pick up strong signals of positive selection. Here, we present a new method for identifying adaptive evolution on short evolutionary time scales with densely-sampled populations. We apply this method to SARS-CoV-2 to perform a comprehensive analysis of adaptively-evolving regions of the genome. We find that spike S1 is a focal point of adaptive evolution, but also identify positively-selected mutations in other genes that are sculpting the evolutionary trajectory of SARS-CoV-2. Protein-coding mutations in S1 are temporally-clustered and, in 2021, the ratio of nonsynonymous to synonymous divergence in S1 is more than 4 times greater than in the equivalent influenza HA1 subunit.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Results text describing Table 1 has been updated to mention the high substitution rate in ORF8

  • https://github.com/blab/sarscov2-adaptive-evolution

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.
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Posted September 14, 2021.
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Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2
Kathryn E. Kistler, John Huddleston, Trevor Bedford
bioRxiv 2021.09.11.459844; doi: https://doi.org/10.1101/2021.09.11.459844
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Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2
Kathryn E. Kistler, John Huddleston, Trevor Bedford
bioRxiv 2021.09.11.459844; doi: https://doi.org/10.1101/2021.09.11.459844

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