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

      1 , , 2 , 3 , 3 , 2 , 3 , 2 , 3 , 3 , 3 , 3 , 3 , NGS-SA , 4 , & , COVID-19 Genomics UK (COG-UK) , 5 , $ , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 13 , 3 , 14 , , 2 ,
      Published by Elsevier Inc.
      COVID 19, evolutionary adaptation, positive selection, directional selection, recurrent mutations, convergent mutations, diversifying selection, immune evasion, transmission advantage, lineage-defining mutations

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          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 favoured 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.


          An analysis of synonymous and non-synonymous mutations in SARS-CoV-2 genomes since the inception of the COVID-19 pandemic provides insights into the emergence of a convergent mutational signature in the 501Y lineage (alpha, beta and gamma variants) that is also likely present in other lineages that impacts host immune recognition.

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          Author and article information

          Published by Elsevier Inc.
          7 September 2021
          7 September 2021
          [1 ]Institute of Infectious Diseases and Molecular Medicine, Division Of Computational Biology, Department of Integrative Biomedical Sciences, University of Cape Town, 7701, South Africa
          [2 ]Institute for Genomics and Evolutionary Medicine, Department of Biology, Temple University, Pennsylvania, 19122, USA
          [3 ]KwaZulu-Natal Research Innovation and Sequencing Platform, School of Laboratory Medicine & Medical Sciences, University of KwaZulu- Natal, Durban, 4001, South Africa
          [6 ]Clinical Microbiology, University of Cambridge, Cambridge, CB2 1TN, UK
          [7 ]Africa Health Research Institute, KwaZulu-Natal, 4013, South Africa
          [8 ]Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
          [9 ]Department of Biochemistry and Molecular Biology, The Pennsylvania State University, Pennsylvania, 16802, USA
          [10 ]Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 141 83, Sweden
          [11 ]South African Medical Research Council Capacity Development Unit, South African National Bioinformatics Institute, University of the Western Cape, Bellville, 7635, South Africa
          [12 ]Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, 3000, Belgium
          [13 ]MRC-University of Glasgow Centre for Virus Research, G12 8QQ, Scotland, UK
          [14 ]Department of Global Health, University of Washington, Seattle, 98195-4550, USA
          Author notes
          []Corresponding author e-mail addresses, Darren P Martin: de Oliveira: L Kosakovsky Pond:

          Full list of consortium names and affiliations are in Appendix 1


          Full list of consortium names and affiliations are in Appendix 2

          © 2021 Published by Elsevier Inc.

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.


          Cell biology
          covid 19,evolutionary adaptation,positive selection,directional selection,recurrent mutations,convergent mutations,diversifying selection,immune evasion,transmission advantage,lineage-defining mutations


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