A selective sweep in the Spike gene has driven SARS-CoV-2 human adaptation

dc.contributor.authorKang, Linen
dc.contributor.authorHe, Guijuanen
dc.contributor.authorSharp, Amanda K.en
dc.contributor.authorWang, Xiaofengen
dc.contributor.authorBrown, Anne M.en
dc.contributor.authorMichalak, Pawelen
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.date.accessioned2021-12-15T01:53:07Zen
dc.date.available2021-12-15T01:53:07Zen
dc.date.issued2021-08-19en
dc.date.updated2021-12-15T01:53:02Zen
dc.description.abstractThe coronavirus disease 2019 (COVID-19) pandemic underscores the need to better understand animal-to-human transmission of coronaviruses and adaptive evolution within new hosts. We scanned more than 182,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes for selective sweep signatures and found a distinct footprint of positive selection located around a non-synonymous change (A1114G; T372A) within the spike protein receptor-binding domain (RBD), predicted to remove glycosylation and increase binding to human ACE2 (hACE2), the cellular receptor. This change is present in all human SARS-CoV-2 sequences but not in closely related viruses from bats and pangolins. As predicted, T372A RBD bound hACE2 with higher affinity in experimental binding assays. We engineered the reversion mutant (A372T) and found that A372 (wild-type [WT]-SARS-CoV-2) enhanced replication in human lung cells relative to its putative ancestral variant (T372), an effect that was 20 times greater than the well-known D614G mutation. Our findings suggest that this mutation likely contributed to SARS-CoV-2 emergence from animal reservoirs or enabled sustained human-to-human transmission.en
dc.description.versionPublished versionen
dc.format.extentPages 4392-+en
dc.format.extent13 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.cell.2021.07.007en
dc.identifier.eissn1097-4172en
dc.identifier.issn0092-8674en
dc.identifier.issue17en
dc.identifier.orcidWang, Xiaofeng [0000-0002-3850-3274]en
dc.identifier.orcidBrown, Anne M. [0000-0001-6951-8228]en
dc.identifier.otherS0092-8674(21)00833-3 (PII)en
dc.identifier.pmid34289344en
dc.identifier.urihttp://hdl.handle.net/10919/106999en
dc.identifier.volume184en
dc.language.isoenen
dc.publisherCell Pressen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000686554600005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectLife Sciences & Biomedicineen
dc.subjectBiochemistry & Molecular Biologyen
dc.subjectCell Biologyen
dc.subjectTO-HUMAN TRANSMISSIONen
dc.subjectWEST-NILE-VIRUSen
dc.subjectSARS-CORONAVIRUSen
dc.subjectBAT CORONAVIRUSen
dc.subjectEBOLA-VIRUSen
dc.subjectCELL ENTRYen
dc.subjectZIKA VIRUSen
dc.subjectIDENTIFICATIONen
dc.subjectINFECTIVITYen
dc.subjectPREDICTIONen
dc.subjectCOVID-19en
dc.subjectSARS-CoV-2en
dc.subjectemergenceen
dc.subjectmolecular virologyen
dc.subjectselective sweepen
dc.subjectspilloveren
dc.subjectviral adaptationen
dc.subject06 Biological Sciencesen
dc.subject11 Medical and Health Sciencesen
dc.subjectDevelopmental Biologyen
dc.subject.meshCell Lineen
dc.subject.meshVero Cellsen
dc.subject.meshAnimalsen
dc.subject.meshChiropteraen
dc.subject.meshHumansen
dc.subject.meshAmino Acid Substitutionen
dc.subject.meshDisease Reservoirsen
dc.subject.meshEvolution, Molecularen
dc.subject.meshPhylogenyen
dc.subject.meshMutationen
dc.subject.meshGenome, Viralen
dc.subject.meshModels, Molecularen
dc.subject.meshSpike Glycoprotein, Coronavirusen
dc.subject.meshChlorocebus aethiopsen
dc.subject.meshCOVID-19en
dc.subject.meshAngiotensin-Converting Enzyme 2en
dc.subject.meshSARS-CoV-2en
dc.titleA selective sweep in the Spike gene has driven SARS-CoV-2 human adaptationen
dc.title.serialCellen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2021-07-02en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/School of Plant and Environmental Sciencesen
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