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Cited by 1,006SARS-CoV-2 and COVID-19 ResearchEvolution and Genetic DynamicsCOVID-19 epidemiological studies

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

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Volz, Erik, Hill, Verity, McCrone, John T., Price, Anna, Jorgensen, David, O’Toole, Áine, Southgate, Joel, Johnson, Robert +573 more·2021·Cell
DOI 10.1016/j.cell.2020.11.020PMC PMC7674007

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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 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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  • Mutations in SARS-CoV-2 could confer advantage by increased transmissibility or escape from innate or acquired immune responses.

    “Mutations could confer advantage to the virus in a number of ways, but increased transmissibility or escape from innate or acquired immune responses are two potential examples (Volz et al., 2021).”

    From Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum (2021) · cites this paper as Volz et al., 2021

  • Mutations in S may give SARS-CoV-2 a selective advantage through increased efficiency of transmission or escape from neutralizing antibodies.

    “concentrating on mutation in S, there are two clear possibilities: increased efficiency of transmission and escape from neutralizing antibodies”

    From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Volz et al., 2021

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  1. Furuyama T.N. Antoneli F. Carvalho I.M.V.G. Briones M.R.S. Janini L.M.R. Temporal data series of COVID-19 epidemics in the USA, Asia and Europe suggests a selective sweep of SARS-CoV-2 Spike D614G variant arXiv 2020 2006.11609

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Volz, E., Hill, V., McCrone, J. T., Price, A., Jorgensen, D., O’Toole, Á., Southgate, J., Johnson, R., Jackson, B., Nascimento, F. F., Rey, S. M., Nicholls, S. M., Colquhoun, R. M., da Silva Filipe, A., Shepherd, J., Pascall, D. J., Shah, R., Jesudason, N., Li, K., Jarrett, R., Pacchiarini, N., Bull, M., Geidelberg, L., Siveroni, I., Koshy, C., Wise, E., Cortes, N., Lynch, J., Kidd, S., Mori, M., Fairley, D. J., Curran, T., McKenna, J. P., Adams, H., Fraser, C., Golubchik, T., Bonsall, D., Moore, C., Caddy, S. L., Khokhar, F. A., Wantoch, M., Reynolds, N., Warne, B., Maksimovic, J., Spellman, K., McCluggage, K., John, M., Beer, R., Afifi, S., Morgan, S., Marchbank, A., Price, A., Kitchen, C., Gulliver, H., Merrick, I., Southgate, J., Guest, M., Munn, R., Workman, T., Connor, T. R., Fuller, W., Bresner, C., Snell, L. B., Charalampous, T., Nebbia, G., Batra, R., Edgeworth, J., Robson, S. C., Beckett, A., Loveson, K. F., Aanensen, D. M., Underwood, A. P., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Clark, G., Smith, W., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Berry, L., Boswell, T., Joseph, A., Willingham, I., Bird, P., Helmer, T., Fallon, K., Holmes, C., Tang, J., Raviprakash, V., Campbell, S., Sheriff, N., Loose, M. W., Holmes, N., Moore, C., Carlile, M., Wright, V., Sang, F., Debebe, J., Coll, F., Signell, A. W., Betancor, G., Wilson, H. D., Feltwell, T., Houldcroft, C. J., Eldirdiri, S., Kenyon, A., Davis, T., Pybus, O., du Plessis, L., Zarebski, A., Raghwani, J., Kraemer, M., Francois, S., Attwood, S., Vasylyeva, T., Torok, M. E., Hamilton, W. L., Goodfellow, I. G., Hall, G., Jahun, A. S., Chaudhry, Y., Hosmillo, M., Pinckert, M. L., Georgana, I., Yakovleva, A., Meredith, L. W., Moses, S., Lowe, H., Ryan, F., Fisher, C. L., Awan, A. R., Boyes, J., Breuer, J., Harris, K. A., Brown, J. R., Shah, D., Atkinson, L., Lee, J. C. D., Alcolea-Medina, A., Moore, N., Cortes, N., Williams, R., Chapman, M. R., Levett, L. J., Heaney, J., Smith, D. L., Bashton, M., Young, G. R., Allan, J., Loh, J., Randell, P. A., Cox, A., Madona, P., Holmes, A., Bolt, F., Price, J., Mookerjee, S., Rowan, A., Taylor, G. P., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Siveroni, I., Johnson, R., Boyd, O., Geidelberg, L., Volz, E. M., Brunker, K., Smollett, K. L., Loman, N. J., Quick, J., McMurray, C., Stockton, J., Nicholls, S., Rowe, W., Poplawski, R., Martinez-Nunez, R. T., Mason, J., Robinson, T. I., O'Toole, E., Watts, J., Breen, C., Cowell, A., Ludden, C., Sluga, G., Machin, N. W., Ahmad, S. S. Y., George, R. P., Halstead, F., Sivaprakasam, V., Thomson, E. C., Shepherd, J. G., Asamaphan, P., Niebel, M. O., Li, K. K., Shah, R. N., Jesudason, N. G., Parr, Y. A., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Nomikou, K., Aranday-Cortes, E., Johnson, N., Starinskij, I., da Silva Filipe, A., Robertson, D. L., Orton, R. J., Hughes, J., Vattipally, S., Singer, J. B., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Taha, Y., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Collins, J., Eltringham, G., Templeton, K. E., McHugh, M. P., Dewar, R., Wastenge, E., Dervisevic, S., Stanley, R., Prakash, R., Stuart, C., Elumogo, N., Sethi, D. K., Meader, E. J., Coupland, L. J., Potter, W., Graham, C., Barton, E., Padgett, D., Scott, G., Swindells, E., Greenaway, J., Nelson, A., Yew, W. C., Resende Silva, P. C., Andersson, M., Shaw, R., Peto, T., Justice, A., Eyre, D., Crooke, D., Hoosdally, S., Sloan, T. J., Duckworth, N., Walsh, S., Chauhan, A. J., Glaysher, S., Bicknell, K., Wyllie, S., Butcher, E., Elliott, S., Lloyd, A., Impey, R., Levene, N., Monaghan, L., Bradley, D. T., Allara, E., Pearson, C., Muir, P., Vipond, I. B., Hopes, R., Pymont, H. M., Hutchings, S., Curran, M. D., Parmar, S., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Chand, M., Dabrera, G., Ramsay, M., Bradshaw, D., Thornton, A., Myers, R., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Harrison, I., Hartman, H., Manesis, N., Patel, V., Bishop, C., Chalker, V., Osman, H., Bosworth, A., Robinson, E., Holden, M. T. G., Shaaban, S., Birchley, A., Adams, A., Davies, A., Gaskin, A., Plimmer, A., Gatica-Wilcox, B., McKerr, C., Moore, C., Williams, C., Heyburn, D., De Lacy, E., Hilvers, E., Downing, F., Shankar, G., Jones, H., Asad, H., Coombes, J., Watkins, J., Evans, J. M., Fina, L., Gifford, L., Gilbert, L., Graham, L., Perry, M., Morgan, M., Bull, M., Cronin, M., Pacchiarini, N., Craine, N., Jones, R., Howe, R., Corden, S., Rey, S., Kumziene-Summerhayes, S., Taylor, S., Cottrell, S., Jones, S., Edwards, S., O’Grady, J., Page, A. J., Wain, J., Webber, M. A., Mather, A. E., Baker, D. J., Rudder, S., Yasir, M., Thomson, N. M., Aydin, A., Tedim, A. P., Kay, G. L., Trotter, A. J., Gilroy, R. A. J., Alikhan, N.-F., de Oliveira Martins, L., Le-Viet, T., Meadows, L., Kolyva, A., Diaz, M., Bell, A., Gutierrez, A. V., Charles, I. G., Adriaenssens, E. M., Kingsley, R. A., Casey, A., Simpson, D. A., Molnar, Z., Thompson, T., Acheson, E., Masoli, J. A. H., Knight, B. A., Hattersley, A., Ellard, S., Auckland, C., Mahungu, T. W., Irish-Tavares, D., Haque, T., Bourgeois, Y., Scarlett, G. P., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Liggett, S., Baker, P., Essex, S., Lyons, R. A., Caller, L. G., Castellano, S., Williams, R. J., Kristiansen, M., Roy, S., Williams, C. A., Dyal, P. L., Tutill, H. J., Panchbhaya, Y. N., Forrest, L. M., Niola, P., Findlay, J., Brooks, T. T., Gavriil, A., Mestek-Boukhibar, L., Weeks, S., Pandey, S., Berry, L., Jones, K., Richter, A., Beggs, A., Smith, C. P., Bucca, G., Hesketh, A. R., Harrison, E. M., Peacock, S. J., Palmer, S., Churcher, C. M., Bellis, K. L., Girgis, S. T., Naydenova, P., Blane, B., Sridhar, S., Ruis, C., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Kermack, L. M., Hadjirin, N. F., Aggarwal, D., Griffith, L., Swingler, T., Davidson, R. K., Rambaut, A., Williams, T., Balcazar, C. E., Gallagher, M. D., O'Toole, Á., Rooke, S., Jackson, B., Colquhoun, R., Ashworth, J., Hill, V., McCrone, J. T., Scher, E., Yu, X., Williamson, K. A., Stanton, T. D., Michell, S. L., Bewshea, C. M., Temperton, B., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Jeffries, A. R., Darby, A. C., Hiscox, J. A., Paterson, S., Iturriza-Gomara, M., Jackson, K. A., Lucaci, A. O., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Turtle, L., Haldenby, S. T., Gregory, R., Gemmell, M., Kwiatkowski, D., de Silva, T. I., Smith, N., Angyal, A., Lindsey, B. B., Groves, D. C., Green, L. R., Wang, D., Freeman, T. M., Parker, M. D., Keeley, A. J., Parsons, P. J., Tucker, R. M., Brown, R., Wyles, M., Constantinidou, C., Unnikrishnan, M., Ott, S., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Stark, R., Baxter, L., Alam, M. T., Brown, P. E., McClure, P. C., Chappell, J. G., Tsoleridis, T., Ball, J., Grammatopoulos, D., Buck, D., Todd, J. A., Green, A., Trebes, A., MacIntyre-Cockett, G., de Cesare, M., Langford, C., Alderton, A., Amato, R., Goncalves, S., Jackson, D. K., Johnston, I., Sillitoe, J., Palmer, S., Lawniczak, M., Berriman, M., Danesh, J., Livett, R., Shirley, L., Farr, B., Quail, M., Thurston, S., Park, N., Betteridge, E., Weldon, D., Goodwin, S., Nelson, R., Beaver, C., Letchford, L., Jackson, D. A., Foulser, L., McMinn, L., Prestwood, L., Kay, S., Kane, L., Dorman, M. J., Martincorena, I., Puethe, C., Keatley, J.-P., Tonkin-Hill, G., Smith, C., Jamrozy, D., Beale, M. A., Patel, M., Ariani, C., Spencer-Chapman, M., Drury, E., Lo, S., Rajatileka, S., Scott, C., James, K., Buddenborg, S. K., Berger, D. J., Patel, G., Garcia-Casado, M. V., Dibling, T., McGuigan, S., Rogers, H. A., Hunter, A. D., Souster, E., Neaverson, A. S., Goodfellow, I., Loman, N. J., Pybus, O. G., Robertson, D. L., Thomson, E. C., Rambaut, A., & Connor, T. R.
Affiliations
  • Imperial College London (GB)
  • University of Birmingham (GB)
  • University of Glasgow (GB)
  • MRC University of Glasgow Centre for Virus Research (GB)
  • University of Cambridge (GB)
  • Royal Veterinary College (GB)
  • University of Edinburgh (GB)
  • Quadram Institute (GB)
  • Cardiff University (GB)
  • Public Health Wales (GB)
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2021-01
Volume
184
Issue
1
Pages
64-75.e11
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2020.11.020
PMC
PMC7674007
OpenAlex
W3098697637
Cited by
1,006
References
63
Citations by year
2026: 23 · 2025: 36 · 2024: 75 · 2023: 128 · 2022: 290 · 2021: 423 · 2020: 30
FWCI
28.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Northumbria Research Link (Northumbria University) (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion, cc-by)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Acceda (Universidad de Las Palmas de Gran Canaria) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Lund University Publications (Lund University) (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
  • UEA Digital Repository (University of East Anglia) (submittedVersion)
  • Apollo (cc-by)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/R012504/1, BB/M010996/1, BB/M009122/1)
  • European Commission (101003653)
  • Wellcome Trust (206298/Z/17/Z)
  • European Regional Development Fund
  • Medical Research Council (MR/L015080/1, MR/R015600/1, MC_UU_1201412)
  • Llywodraeth Cymru
  • CANDU Owners Group
  • European Research Council (725422)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
Keywords
SARS-CoV-2, spike protein, D614G mutation, positive selection, founder effect, viral transmissibility, pathogenicity, COVID-19 mortality, viral load, population genetics, phylogenetic clusters, United Kingdom
MeSH terms
Whole Genome Sequencing, COVID-19, SARS-CoV-2, Aspartic Acid, Glycine, United Kingdom, Humans, Mutation, Virulence, Genome, Viral, Amino Acid Substitution, Spike Glycoprotein, Coronavirus

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