Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution

PLoS One. 2022 May 24;17(5):e0268389. doi: 10.1371/journal.pone.0268389. eCollection 2022.

Abstract

Nearly two decades after the last epidemic caused by a severe acute respiratory syndrome coronavirus (SARS-CoV), newly emerged SARS-CoV-2 quickly spread in 2020 and precipitated an ongoing global public health crisis. Both the continuous accumulation of point mutations, owed to the naturally imposed genomic plasticity of SARS-CoV-2 evolutionary processes, as well as viral spread over time, allow this RNA virus to gain new genetic identities, spawn novel variants and enhance its potential for immune evasion. Here, through an in-depth phylogenetic clustering analysis of upwards of 200,000 whole-genome sequences, we reveal the presence of previously unreported and hitherto unidentified mutations and recombination breakpoints in Variants of Concern (VOC) and Variants of Interest (VOI) from Brazil, India (Beta, Eta and Kappa) and the USA (Beta, Eta and Lambda). Additionally, we identify sites with shared mutations under directional evolution in the SARS-CoV-2 Spike-encoding protein of VOC and VOI, tracing a heretofore-undescribed correlation with viral spread in South America, India and the USA. Our evidence-based analysis provides well-supported evidence of similar pathways of evolution for such mutations in all SARS-CoV-2 variants and sub-lineages. This raises two pivotal points: (i) the co-circulation of variants and sub-lineages in close evolutionary environments, which sheds light onto their trajectories into convergent and directional evolution, and (ii) a linear perspective into the prospective vaccine efficacy against different SARS-CoV-2 strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil / epidemiology
  • COVID-19* / epidemiology
  • Cluster Analysis
  • Humans
  • Mutation
  • Phylogeny
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This work was supported by the Fundação de Amparo à Pesquisa doEstado384 de São Paulo (FAPESP), Brazil, grants 2019/01255-9 and 2021/03684-4(Young385 Investigator Program) (RD-C), and by the Conselho Nacional de Desenvolvimento386 Científico e Tecnológico (CNPq), Brazil, grant 405691/2018-1 (C.T.B). DRNis387 recipient of an institutional scholarship from the Coordenação de Aperfeiçoamento388 de Pessoal de Nível Superior (CAPES), Brazil, grant 88887.506234/2020-00.