Imperial College London
Professor Robert Wilkinson

ProfessorRobertWilkinson

Faculty of Medicine, Department of Infectious Disease

Professor in Infectious Diseases
 
 
 
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Contact

 

r.j.wilkinson Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Martin:2022:molbev/msac061,
author = {Martin, DP and Spyros, L and Lucaci, AG and Maier, W and Gruning, B and Shank, SD and Weaver, S and MacLean, OA and Orton, RJ and Lemey, P and Boni, MF and Tegally, H and Harkins, GW and Scheepers, C and Bhiman, JN and Everatt, J and Amoako, DG and San, JE and Giandhari, J and Sigal, A and Williamson, C and Hsiao, N-Y and von, Gottberg A and De, Klerk A and Shafer, RW and Robertson, DL and Wilkinson, RJ and Sewell, TS and Lessells, R and Nekrutenko, A and Greaney, AJ and Starr, TN and Bloom, JD and Murrell, B and Wilkinson, E and Gupta, RK and de, Oliveira T and Kosakovsky, Pond SL},
doi = {molbev/msac061},
journal = {Molecular Biology and Evolution},
title = {Selection analysis identifies clusters of unusual mutational changes in Omicron lineage BA.1 that likely impact Spike function},
url = {http://dx.doi.org/10.1093/molbev/msac061},
volume = {39},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations inintrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related  sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore coperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
AU  - Martin,DP
AU  - Spyros,L
AU  - Lucaci,AG
AU  - Maier,W
AU  - Gruning,B
AU  - Shank,SD
AU  - Weaver,S
AU  - MacLean,OA
AU  - Orton,RJ
AU  - Lemey,P
AU  - Boni,MF
AU  - Tegally,H
AU  - Harkins,GW
AU  - Scheepers,C
AU  - Bhiman,JN
AU  - Everatt,J
AU  - Amoako,DG
AU  - San,JE
AU  - Giandhari,J
AU  - Sigal,A
AU  - Williamson,C
AU  - Hsiao,N-Y
AU  - von,Gottberg A
AU  - De,Klerk A
AU  - Shafer,RW
AU  - Robertson,DL
AU  - Wilkinson,RJ
AU  - Sewell,TS
AU  - Lessells,R
AU  - Nekrutenko,A
AU  - Greaney,AJ
AU  - Starr,TN
AU  - Bloom,JD
AU  - Murrell,B
AU  - Wilkinson,E
AU  - Gupta,RK
AU  - de,Oliveira T
AU  - Kosakovsky,Pond SL
DO  - molbev/msac061
PY  - 2022///
SN  - 0737-4038
TI  - Selection analysis identifies clusters of unusual mutational changes in Omicron lineage BA.1 that likely impact Spike function
T2  - Molecular Biology and Evolution
UR  - http://dx.doi.org/10.1093/molbev/msac061
UR  - http://hdl.handle.net/10044/1/96141
VL  - 39
ER  -
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