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.
| Original language | English |
|---|---|
| Pages (from-to) | 64-75.e11 |
| Journal | Cell |
| Volume | 184 |
| Issue number | 1 |
| Early online date | 18 Nov 2020 |
| DOIs | |
| Publication status | Published - 7 Jan 2021 |
Keywords
- COVID-19
- epidemiology
- evolution
- founder effect
- SARS-CoV-2
- spike
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Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity. / Colquhoun, Rachel M.; da Silva Filipe, Ana; Shepherd, James et al.
In: Cell, Vol. 184, No. 1, 07.01.2021, p. 64-75.e11.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity
AU - Volz, Erik
AU - Hill, Verity
AU - McCrone, John T.
AU - Price, Anna
AU - Jorgensen, David
AU - O'Toole, Áine
AU - Southgate, Joel
AU - Johnson, Robert
AU - Jackson, Ben
AU - Nascimento, Fabricia F.
AU - Rey, Sara M.
AU - Nicholls, Samuel M.
AU - Colquhoun, Rachel M.
AU - da Silva Filipe, Ana
AU - Shepherd, James
AU - Pascall, David J.
AU - Shah, Rajiv
AU - Jesudason, Natasha
AU - Li, Kathy
AU - Jarrett, Ruth
AU - Pacchiarini, Nicole
AU - Bull, Matthew
AU - Geidelberg, Lily
AU - Siveroni, Igor
AU - COG-UK Consortium
AU - Goodfellow, Ian
AU - Loman, Nicholas J.
AU - Pybus, Oliver G.
AU - Robertson, David L.
AU - Thomson, Emma C.
AU - Rambaut, Andrew
AU - Connor, Thomas R.
AU - Davidson, Rosemary
N1 - Funding Information: We thank all partners and contributors to the COG-UK consortium who are listed at https://www.cogconsortium.uk/about/ . We also acknowledge the important work of SARS-CoV-2 genome data producers globally contributing sequence data to the GISAID database and particularly acknowledge the groups who have generated data used by this project, listed in Table S4 . E.V. acknowledges the MRC Centre for Global Infectious Disease Analysis ( MR/R015600/1 ). R. Johnson and E.V. acknowledge funding from the European Commission (CoroNAb 101003653 ). V.H. was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (grant no. BB/M010996/1 ). J.T.M., R.M.C., N.J.L., and A.R. acknowledge the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z – ARTIC network). A.R. is supported by the European Research Council (grant agreement no. 725422 – ReservoirDOCS). D.L.R., A.d.S.F., and E.C.T. are supported by the MRC ( MC_UU_1201412 ). J. Southgate was supported by the BBSRC -funded South West Biosciences Doctoral Training Partnership (training grant reference BB/M009122/1 ). T.R.C. and N.J.L. acknowledge support from the MRC , which funded computational resources used by the project (grant reference MR/L015080/1 ). T.R.C. acknowledges funding as part of the BBSRC Institute Strategic Programme Microbes in the Food Chain ( BB/R012504/1 ) and its constituent projects ( BBS/E/F/000PR10348 and BBS/E/F/000PR10352 ). A.P. and T.R.C. acknowledge support from Supercomputing Wales , which is partially funded by the European Regional Development Fund (ERDF) via Welsh Government . The project was also supported by specific funding from Welsh Government , which provided funds for the sequencing and analysis of a subset of the Welsh samples used in this study, via Genomics Partnership Wales. Funding Information: We thank all partners and contributors to the COG-UK consortium who are listed at https://www.cogconsortium.uk/about/. We also acknowledge the important work of SARS-CoV-2 genome data producers globally contributing sequence data to the GISAID database and particularly acknowledge the groups who have generated data used by this project, listed in Table S4. E.V. acknowledges the MRC Centre for Global Infectious Disease Analysis (MR/R015600/1). R. Johnson and E.V. acknowledge funding from the European Commission (CoroNAb 101003653). V.H. was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (grant no. BB/M010996/1). J.T.M. R.M.C. N.J.L. and A.R. acknowledge the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z ? ARTIC network). A.R. is supported by the European Research Council (grant agreement no. 725422 ? ReservoirDOCS). D.L.R. A.d.S.F. and E.C.T. are supported by the MRC (MC_UU_1201412). J. Southgate was supported by the BBSRC-funded South West Biosciences Doctoral Training Partnership (training grant reference BB/M009122/1). T.R.C. and N.J.L. acknowledge support from the MRC, which funded computational resources used by the project (grant reference MR/L015080/1). T.R.C. acknowledges funding as part of the BBSRC Institute Strategic Programme Microbes in the Food Chain (BB/R012504/1) and its constituent projects (BBS/E/F/000PR10348 and BBS/E/F/000PR10352). A.P. and T.R.C. acknowledge support from Supercomputing Wales, which is partially funded by the European Regional Development Fund (ERDF) via Welsh Government. The project was also supported by specific funding from Welsh Government, which provided funds for the sequencing and analysis of a subset of the Welsh samples used in this study, via Genomics Partnership Wales. Conceptualization, E.V. N.J.L. A.R. and T.R.C.; Data Generation, S.M.R. J. Shepherd, R.S. K.L. N.P. M.B. D.L.R. E.C.T. and COG-UK; Methodology, E.V. J. Southgate, D.J.P. R.S. K.L. R. Jarrett, E.C.T. and A.R.; Software, E.V. S.M.N. M.B. I.S. and A.R.; Analysis, E.V. V.H. J.T.M. A.P. A.O. J. Southgate. S.M.R. J. Shepherd. D.J.P. L.G. O.G.P. E.C.T. A.R. and T.R.C.; Writing ? Original Draft, E.V. V.H. J.T.M. A.P. F.F.N. A.R. and T.R.C.; Writing ? Review & Editing, D.J. B.J. F.F.N. A.d.S.F. N.J. L.G. I.G. N.J.L. O.G.P. D.L.R. and E.C.T.; Visualization, E.V. V.H. A.P. D.J. A.O. R. Johnson, J. Shepherd, and A.R.; Supervision, E.V. N.J.L. D.L.R. E.C.T. A.R. and T.R.C.; Funding Acquisition, E.V. N.J.L. E.C.T. A.R. and T.R.C. The authors declare no competing interests.
PY - 2021/1/7
Y1 - 2021/1/7
N2 - 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.
AB - 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.
KW - COVID-19
KW - epidemiology
KW - evolution
KW - founder effect
KW - SARS-CoV-2
KW - spike
UR - http://www.scopus.com/inward/record.url?scp=85098925617&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.11.020
DO - 10.1016/j.cell.2020.11.020
M3 - Article
AN - SCOPUS:85098925617
VL - 184
SP - 64-75.e11
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -