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Investigating the evolutionary origins of the first three SARS-CoV-2 variants of concern

View ORCID ProfileMahan Ghafari, Qihan Liu, Arushi Dhillon, Aris Katzourakis, Daniel B Weissman
doi: https://doi.org/10.1101/2022.05.09.491227
Mahan Ghafari
1Department of Zoology, University of Oxford, Oxford, UK
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Qihan Liu
2Department of Physics, Emory University, Atlanta, Georgia, US
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Arushi Dhillon
2Department of Physics, Emory University, Atlanta, Georgia, US
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Aris Katzourakis
1Department of Zoology, University of Oxford, Oxford, UK
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  • For correspondence: daniel.weissman@emory.edu aris.katzourakis@zoo.ox.ac.uk
Daniel B Weissman
2Department of Physics, Emory University, Atlanta, Georgia, US
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  • For correspondence: daniel.weissman@emory.edu aris.katzourakis@zoo.ox.ac.uk
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Abstract

The emergence of Variants of Concern (VOCs) of SARS-CoV-2 with increased transmissibility, immune evasion properties, and virulence poses a great challenge to public health. Despite unprecedented efforts to increase genomic surveillance, fundamental facts about the evolutionary origins of VOCs remain largely unknown. One major uncertainty is whether the VOCs evolved during transmission chains of many acute infections or during long-term infections within single individuals. We test the consistency of these two possible paths with the observed dynamics, focusing on the clustered emergence of the first three VOCs, Alpha, Beta, and Gamma, in late 2020, following a period of relative evolutionary stasis. We consider a range of possible fitness landscapes, in which the VOC phenotypes could be the result of single mutations, multiple mutations that each contribute additively to increasing viral fitness, or epistatic interactions among multiple mutations that do not individually increase viral fitness—a “fitness plateau”. Our results suggest that the timing and dynamics of the VOC emergence, together with the observed number of mutations in VOC lineages, are in best agreement with the VOC phenotype requiring multiple mutations and VOCs having evolved within single individuals with long-term infections.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/weissmanlab/Valley_Crossing

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 4.0 International license.
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Posted May 11, 2022.
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Investigating the evolutionary origins of the first three SARS-CoV-2 variants of concern
Mahan Ghafari, Qihan Liu, Arushi Dhillon, Aris Katzourakis, Daniel B Weissman
bioRxiv 2022.05.09.491227; doi: https://doi.org/10.1101/2022.05.09.491227
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Investigating the evolutionary origins of the first three SARS-CoV-2 variants of concern
Mahan Ghafari, Qihan Liu, Arushi Dhillon, Aris Katzourakis, Daniel B Weissman
bioRxiv 2022.05.09.491227; doi: https://doi.org/10.1101/2022.05.09.491227

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