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Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Volz, Erik ; Hill, Verity ; McCrone, John T ; Price, Anna ; Jorgensen, David ; O'Toole, Áine ; Southgate, Joel ; Johnson, Robert ; Jackson, Ben and Nascimento, Fabricia F , et al. (2021) In Cell 184(1). p.11-75
Abstract

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical... (More)

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

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LU
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amino Acid Substitution, Aspartic Acid/analysis, COVID-19/epidemiology, Genome, Viral, Glycine/analysis, Humans, Mutation, SARS-CoV-2/genetics, Spike Glycoprotein, Coronavirus/genetics, United Kingdom/epidemiology, Virulence, Whole Genome Sequencing
in
Cell
volume
184
issue
1
pages
11 - 75
publisher
Cell Press
external identifiers
  • pmid:33275900
  • scopus:85098925617
ISSN
1097-4172
DOI
10.1016/j.cell.2020.11.020
language
English
LU publication?
yes
id
b6d57e41-d7fc-4a42-9915-4a40c17f4522
date added to LUP
2021-04-11 20:07:51
date last changed
2025-11-03 07:47:25
@article{b6d57e41-d7fc-4a42-9915-4a40c17f4522,
  abstract     = {{<p>Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.</p>}},
  author       = {{Volz, Erik and Hill, Verity and McCrone, John T and Price, Anna and Jorgensen, David and O'Toole, Áine and Southgate, Joel and Johnson, Robert and Jackson, Ben and Nascimento, Fabricia F and Rey, Sara M and Nicholls, Samuel M and Colquhoun, Rachel M and da Silva Filipe, Ana and Shepherd, James and Pascall, David J and Shah, Rajiv and Jesudason, Natasha and Li, Kathy and Jarrett, Ruth and Pacchiarini, Nicole and Bull, Matthew and Geidelberg, Lily and Siveroni, Igor and Goodfellow, Ian and Loman, Nicholas J and Pybus, Oliver G and Robertson, David L and Thomson, Emma C and Rambaut, Andrew and Connor, Thomas R}},
  issn         = {{1097-4172}},
  keywords     = {{Amino Acid Substitution; Aspartic Acid/analysis; COVID-19/epidemiology; Genome, Viral; Glycine/analysis; Humans; Mutation; SARS-CoV-2/genetics; Spike Glycoprotein, Coronavirus/genetics; United Kingdom/epidemiology; Virulence; Whole Genome Sequencing}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{11--75}},
  publisher    = {{Cell Press}},
  series       = {{Cell}},
  title        = {{Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity}},
  url          = {{http://dx.doi.org/10.1016/j.cell.2020.11.020}},
  doi          = {{10.1016/j.cell.2020.11.020}},
  volume       = {{184}},
  year         = {{2021}},
}