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

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Martin, Darren P 
Weaver, Steven 
Tegally, Houriiyah 
San, James Emmanuel 
Shank, Stephen D 


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.



COVID 19, convergent mutations, directional selection, diversifying selection, evolutionary adaptation, immune evasion, lineage-defining mutations, positive selection, recurrent mutations, transmission advantage, Amino Acid Sequence, COVID-19, Codon, Evolution, Molecular, Genes, Viral, Genetic Drift, Host Adaptation, Humans, Immune Evasion, Mutation, Pandemics, Phylogeny, Public Health, SARS-CoV-2

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Elsevier BV
MRC (MC_PC_19027)
Wellcome Trust (108082/A/15/Z)
UK Research and Innovation (MC_PC_19027)
We gratefully acknowledge all of the authors from the originating laboratories responsible for obtaining the specimens and the submitting laboratories where genetic sequence data were generated and shared via the GISAID Initiative, on which this research is based (Table S5). We thank Carolyn Williamson, Robert Wilkinson, Valarie Mizrahe, Jonathan Blackburn, and Nicola Mulder for reading and commenting on the manuscript. The Wellcome Trust funded D.P.M. (222574/Z/21/Z), D.L.R. (220977/Z/20/Z), P.L. (2206298/Z/17/Z), and O.A.M. (206369/Z/17/Z). The US National Institutes of Health funded S.L.K.P. (R01 AI134384 and AI140970), J.O.W. (R01 AI13599), G.W.H. (1U01Al152151-01), and J.E.S. and H.T. (via H3ABioNet U24HG006941). The US National Science Foundation funded S.L.K.P. (RAPID 2027196 NSF/DBI,BIO), The UK Medical Research Council funded D.L.R. (MC_UU_1201412) and COG-UK (via UK Research & Innovation, the National Institute of Health Research, and Genome Research Limited operating as the Wellcome Sanger Institute). The European Research Council funded P.L. (725422-ReservoirDOCS and 874850-MOOD). The South African Medical Research Council funded NGS-SA via the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council and Department of Science and Innovation.