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Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution

2022-03-29Journal article Open access
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dc.contributor.authorAmicone, M.
dc.contributor.authorBorges, V.
dc.contributor.authorAlves, M.J.
dc.contributor.authorIsidro, J.
dc.contributor.authorZé-Zé, L.
dc.contributor.authorDuarte, S.
dc.contributor.authorGomes, J. P.
dc.contributor.authorGordo, I.
dc.date.accessioned2023-01-25T11:43:43Z
dc.date.available2023-01-25T11:43:43Z
dc.date.issued2022-03-29
dc.descriptionFree PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996265/pt_PT
dc.description.abstractBackground and objectives: To understand how organisms evolve, it is fundamental to study how mutations emerge and establish. Here, we estimated the rate of mutation accumulation of SARS-CoV- 2 in vitro and investigated the repeatability of its evolution when facing a new cell type but no immune or drug pressures. Methodology: We performed experimental evolution with two strains of SARS-CoV-2, one carrying the originally described spike protein (CoV-2-D) and another carrying the D614G mutation that has spread worldwide (CoV-2-G). After 15 passages in Vero cells and whole genome sequencing, we characterized the spectrum and rate of the emerging mutations and looked for evidences of selection across the genomes of both strains. Results: From the frequencies of the mutations accumulated, and excluding the genes with signals of selection, we estimate a spontaneous mutation rate of 1.3 10 6 6 0.2 10 6 per-base per-infection cycle (mean across both lineages of SARS-CoV-262SEM). We further show that mutation accumulation is larger in the CoV-2-D lineage and heterogeneous along the genome, consistent with the action of positive selection on the spike protein, which accumulated five times more mutations than the corresponding genomic average. We also observe the emergence of mutators in the CoV-2-G background, likely linked to mutations in the RNA-dependent RNA polymerase and/or in the error-correcting exonuclease protein. Conclusions and implications: These results provide valuable information on how spontaneous mutations emerge in SARS-CoV-2 and on how selection can shape its genome toward adaptation to new environments. Lay Summary: Each time a virus replicates inside a cell, errors (mutations) occur. Here, via laboratory propagation in cells originally isolated from the kidney epithelium of African green monkeys, we estimated the rate at which the SARS-CoV-2 virus mutates—an important parameter for understanding how it can evolve within and across humans. We also confirm the potential of its Spike protein to adapt to a new environment and report the emergence of mutators—viral populations where mutations occur at a significantly faster rate.pt_PT
dc.description.sponsorshipM.A. was supported by ‘Fundação para a Ciência e Tecnologia’ (FCT), fellowships PD/BD/138735/2018. Research was supported by FCT Project PTDC/BIA-EVL/31528/2017 to I.G. and by funds from Portuguese NIH.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEvol Med Public Health. 2022 Mar 29;10(1):142-155. doi: 10.1093/emph/eoac010. eCollection 2022pt_PT
dc.identifier.doi10.1093/emph/eoac010pt_PT
dc.identifier.issn2050-6201
dc.identifier.urihttp://hdl.handle.net/10400.18/8454
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Press/ on behalf of the Foundation for Evolution, Medicine, and Public Healthpt_PT
dc.relationDiversity and Stability of the Microbiome: an Intertwining Eco-Evolutionary Dynamics
dc.relation.publisherversionhttps://academic.oup.com/emph/article/10/1/142/6555377?login=truept_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectSARS-CoV-2pt_PT
dc.subjectExperimental Evolutionpt_PT
dc.subjectMutation Ratept_PT
dc.subjectMutatorpt_PT
dc.subjectVirus Adaptationpt_PT
dc.subjectInfecções Sistémicas e Zoonosespt_PT
dc.titleMutation rate of SARS-CoV-2 and emergence of mutators during experimental evolutionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDiversity and Stability of the Microbiome: an Intertwining Eco-Evolutionary Dynamics
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F138735%2F2018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-EVL%2F31528%2F2017/PT
oaire.citation.conferencePlaceOxfordpt_PT
oaire.citation.endPage145pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage142pt_PT
oaire.citation.titleEvolution, Medicine, and Public Healthpt_PT
oaire.citation.volume10pt_PT
oaire.fundingStreamOE
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com página web do editor da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationd7ef2d8f-dcde-4ec7-bd73-4376b2a64e05
relation.isProjectOfPublication29b925b8-d1e8-40f5-b70e-99f17d4b91dd
relation.isProjectOfPublication.latestForDiscovery29b925b8-d1e8-40f5-b70e-99f17d4b91dd

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