The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

COVID-19 Genomics UK (COG-UK) Consortium

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55 Citations (Scopus)

Abstract

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organization as Alpha. Originating in early autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK and the imposition of new restrictions, in particular, the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages that preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically infected individual. We conclude that the latter provides the best explanation of the observed behaviour and dynamics of the variant, although the individual need not be immunocompromised, as persistently infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs and find that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations and a lack of the rapid evolutionary rate on its ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms), it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

Original languageEnglish
Article numberveac080
JournalVirus Evolution
Volume8
Issue number2
DOIs
Publication statusPublished - 2022

Bibliographical note

Funding Information:
J.T.M., R.C., and A.R. acknowledge support from the Wellcome Trust (Collaborator Award 206298/Z/17/Z—ARTIC network). O.G.P. and L.D.P. acknowledge support from the Oxford Martin School. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation, the National Institute of Health Research (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. V.H. was supported by the Biotechnology and Biological Sciences Research Council (grant number: BB/M010996/1). T.P.P. and W.S.B. are supported by the G2P-UK National Virology Consortium funded by the MRC (grant number: MR/W005611/1). A.R. is also supported by the European Research Council (grant agreement number: 725422—ReservoirDOCs) and the Bill & Melinda Gates Foundation (OPP1175094—HIV-PANGEA II). A.O.T. is supported by the Wellcome Trust Hosts, Pathogens & Global Health Programme (grant number: grant.203783/Z16/Z), and Fast Grants (award number: 2236). D.A. is a Wellcome Clinical PhD Fellow and gratefully supported by the Wellcome Trust (grant number: 222903/Z/21/Z). I.G. is a Wellcome Senior Fellow and is supported by the Wellcome Trust (grant number: 207498/Z/17/Z). E.V. is supported by the Wellcome Trust (Grant number: 220885/Z/20/Z).

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press.

Keywords

  • SARS-COV-2
  • Virus evolution
  • Within-host evolution
  • variants of concern

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