Rapid Spread of Mutant Alleles in Worldwide SARS-CoV-2 Strains Revealed by Genome-Wide Single Nucleotide Polymorphism and Variation Analysis

Genome Biol Evol. 2021 Feb 3;13(2):evab015. doi: 10.1093/gbe/evab015.

Abstract

The novel coronavirus (SARS-CoV-2) has become a pandemic and is threatening human health globally. Here, we report nine newly evolved SARS-CoV-2 single nucleotide polymorphism (SNP) alleles those underwent a rapid increase (seven cases) or decrease (two cases) in their frequency for 30-80% in the initial four months, which are further confirmed by intrahost single nucleotide variation analysis using raw sequence data including 8,217 samples. The nine SNPs are mostly (8/9) located in the coding region and are mainly (6/9) nonsynonymous substitutions. The nine SNPs show a complete linkage in SNP pairs and belong to three different linkage groups, named LG_1 to LG_3. Analyses in population genetics show signatures of adaptive selection toward the mutants in LG_1, but no signal of selection for LG_2. Population genetic analysis results on LG_3 show geological differentiation. Analyses on geographic COVID-19 cases and published clinical data provide evidence that the mutants in LG_1 and LG_3 benefit virus replication and those in LG_1 have a positive correlation with the disease severity in COVID-19-infected patients. The mutants in LG_2 show a bias toward mildness of the disease based on available public clinical data. Our findings may be instructive for epidemiological surveys and disease control of COVID-19 in the future.

Keywords: COVID-19; SARS-CoV-2; SNP; iSNV; mutants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • COVID-19 / epidemiology
  • COVID-19 / virology*
  • Gene Frequency
  • Genes, Viral
  • Humans
  • Linkage Disequilibrium
  • Mutation*
  • Polymorphism, Single Nucleotide*
  • SARS-CoV-2 / genetics*