The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages

Cell. 2021 Sep 30;184(20):5189-5200.e7. doi: 10.1016/j.cell.2021.09.003. Epub 2021 Sep 7.


The independent emergence late in 2020 of the B.1.1.7, B.1.351, and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three "501Y lineages" coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites, mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.

Keywords: COVID 19; convergent mutations; directional selection; diversifying selection; evolutionary adaptation; immune evasion; lineage-defining mutations; positive selection; recurrent mutations; transmission advantage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • COVID-19 / epidemiology*
  • COVID-19 / immunology
  • COVID-19 / transmission
  • COVID-19 / virology
  • Codon / genetics
  • Evolution, Molecular*
  • Genes, Viral
  • Genetic Drift
  • Host Adaptation / genetics
  • Humans
  • Immune Evasion
  • Mutation*
  • Pandemics*
  • Phylogeny
  • Public Health
  • SARS-CoV-2 / genetics*


  • Codon