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dc.creatorMartin, Darren P.
dc.creatorLytras, Spyros
dc.creatorLucaci, Alexander
dc.creatorMaier, Wolfgang
dc.creatorGrüning, Björn
dc.creatorShank, Stephen
dc.creatorWeaver, Steven
dc.creatorMacLean, Oscar A.
dc.creatorOrton, Richard J.
dc.creatorLemey, Philippe
dc.creatorBoni, Maciej F.
dc.creatorTegally, Houriiyah
dc.creatorHarkins, Gordon
dc.creatorScheepers, Cathrine
dc.creatorBhiman, Jinal N.
dc.creatorEveratt, Josie
dc.creatorAmoako, Daniel G.
dc.creatorSan, James Emmanuel
dc.creatorGiandhari, Jennifer
dc.creatorSigal, Alex
dc.creatorNGS-SA
dc.creatorWilliamson, Carolyn
dc.creatorHsiao, Nei-yuan
dc.creatorGottberg, Anne von
dc.creatorDe Klerk, Arne
dc.creatorShafer, Robert W.
dc.creatorRobertson, David L.
dc.creatorWilkinson, Robert J.
dc.creatorSewell, B. Trevor
dc.creatorLessells, Richard
dc.creatorNekrutenko, Anton
dc.creatorGreaney, Allison J.
dc.creatorStarr, Tyler N.
dc.creatorBloom, Jesse D.
dc.creatorMurrell, Ben
dc.creatorWilkinson, Eduan
dc.creatorGupta, Ravindra K.
dc.creatorOliveira, Tulio de
dc.creatorPond, Sergei
dc.date.accessioned2022-01-26T22:13:47Z
dc.date.available2022-01-26T22:13:47Z
dc.date.issued2022-01-18
dc.identifier.citationDarren P Martin, Spyros Lytras, Alexander G Lucaci, et al. Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function. bioRxiv 2022.01.14.476382; doi: https://doi.org/10.1101/2022.01.14.476382
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/7296
dc.identifier.urihttp://hdl.handle.net/20.500.12613/7317
dc.description.abstractAmong 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 in intrapatient 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 genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and 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.
dc.format.extent36 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofCOVID-19 Research
dc.relation.isreferencedbybioRxiv
dc.rightsAttribution CC BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCOVID-19 (Disease)
dc.titleSelection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function
dc.typeText
dc.type.genrePre-print
dc.contributor.groupInstitute of Genomic and Evolutionary Medicine (iGEM) (Temple University)
dc.description.departmentBiology
dc.relation.doihttps://doi.org/10.1101/2022.01.14.476382
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.creator.orcidLucaci|0000-0002-4896-6088
dc.creator.orcidWeaver|0000-0002-6931-7191
dc.creator.orcidPond|0000-0003-4817-4029
dc.temple.creatorLucaci, Alexander G.
dc.temple.creatorShank, Stephen D.
dc.temple.creatorWeaver, Steven
dc.temple.creatorPond, Sergei L. Kosakovsky
refterms.dateFOA2022-01-26T22:13:47Z


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