Trends of mutation accumulation across global SARS-CoV-2 genomes: Implications for the evolution of the novel coronavirus

Genomics. 2020 Nov;112(6):5331-5342. doi: 10.1016/j.ygeno.2020.11.003. Epub 2020 Nov 5.


To understand SARS-CoV-2 microevolution, this study explored the genome-wide frequency, gene-wise distribution, and molecular nature of all point-mutations detected across its 71,703 RNA-genomes deposited in GISAID till 21 August 2020. Globally, nsp1/nsp2 and orf7a/orf3a were the most mutation-ridden non-structural and structural genes respectively. Phylogeny of 4618 spatiotemporally-representative genomes revealed that entities belonging to the early lineages are mostly spread over Asian countries, including India, whereas the recently-derived lineages are more globally distributed. Of the total 20,163 instances of polymorphism detected across global genomes, 12,594 and 7569 involved transitions and transversions, predominated by cytidine-to-uridine and guanosine-to-uridine conversions, respectively. Positive selection of nonsynonymous mutations (dN/dS >1) in most of the structural, but not the non-structural, genes indicated that SARS-CoV-2 has already harmonized its replication/transcription machineries with the host metabolism, while it is still redefining virulence/transmissibility strategies at the molecular level. Mechanistic bases and evolutionary/pathogenicity-related implications are discussed for the predominant mutation-types.

Keywords: Genome-wide mutations; Microevolution; Nonsynonymous and synonymous mutations; SARS-CoV-2; Transition; Transversion.

MeSH terms

  • Asia
  • Evolution, Molecular*
  • Genome, Viral*
  • Genomics / methods
  • India
  • Mutation Accumulation*
  • Mutation Rate
  • Mutation, Missense
  • Phylogeny
  • SARS-CoV-2 / genetics*
  • Spike Glycoprotein, Coronavirus / genetics
  • Viral Proteins / genetics
  • Viroporin Proteins / genetics


  • ORF3a protein, SARS-CoV-2
  • ORF7a protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Viral Proteins
  • Viroporin Proteins
  • spike protein, SARS-CoV-2