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The emergence of highly fit SARS-CoV-2 variants accelerated by recombination
Michael R Garvin; Erica T Prates; Jonathon Romero; Ashley Cliff; Joao Gabriel Felipe Machado Gazolla; Monica Pickholz; Mirko Pavicic; Daniel Jacobson.
  • Michael R Garvin; Oak Ridge National Laboratory, Computational Systems Biology, Biosciences; National Virtual Biotechnology Laboratory
  • Erica T Prates; Oak Ridge National Laboratory, Computational Systems Biology, Biosciences; National Virtual Biotechnology Laboratory
  • Jonathon Romero; The Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee Knoxville
  • Ashley Cliff; The Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee Knoxville
  • Joao Gabriel Felipe Machado Gazolla; Oak Ridge National Laboratory, Computational Systems Biology, Biosciences; National Virtual Biotechnology Laboratory
  • Monica Pickholz; Department of Physics, Faculty of Exact and Natural Sciences, University of Buenos Aires; Institute of Physics of Buenos Aires (IFBA), CONICET - University of B
  • Mirko Pavicic; Oak Ridge National Laboratory, Computational Systems Biology, Biosciences; National Virtual Biotechnology Laboratory
  • Daniel Jacobson; Oak Ridge National Laboratory, Computational Systems Biology, Biosciences; National Virtual Biotechnology Laboratory
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-454981
ABSTRACT
The SARS-CoV-2 pandemic recently entered an alarming new phase with the emergence of the variants of concern (VOC) and understanding their biology is paramount to predicting future ones. Current efforts mainly focus on mutations in the spike glycoprotein (S), but changes in other regions of the viral proteome are likely key. We analyzed more than 900,000 SARS-CoV-2 genomes with a computational systems biology approach including a haplotype network and protein structural analyses to reveal lineage-defining mutations and their critical functional attributes. Our results indicate that increased transmission is promoted by epistasis, i.e., combinations of mutations in S and other viral proteins. Mutations in the non-S proteins involve immune-antagonism and replication performance, suggesting convergent evolution. Furthermore, adaptive mutations appear in geographically disparate locations, suggesting that either independent, repeat mutation events or recombination among different strains are generating VOC. We demonstrate that recombination is a stronger hypothesis, and may be accelerating the emergence of VOC by bringing together cooperative mutations. This emphasizes the importance of a global response to stop the COVID-19 pandemic.
Texte intégral: Disponible Collection: Preprints Base de données: bioRxiv Les sujets: Variantes langue: Anglais Année: 2021 Type de document: Preprint

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Texte intégral: Disponible Collection: Preprints Base de données: bioRxiv Les sujets: Variantes langue: Anglais Année: 2021 Type de document: Preprint