Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/8454 |
Resumo: | Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996265/ |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolutionSARS-CoV-2Experimental EvolutionMutation RateMutatorVirus AdaptationInfecções Sistémicas e ZoonosesFree PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996265/Background 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.M.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.Oxford University Press/ on behalf of the Foundation for Evolution, Medicine, and Public HealthRepositório Científico do Instituto Nacional de SaúdeAmicone, M.Borges, V.Alves, M.J.Isidro, J.Zé-Zé, L.Duarte, S.Gomes, J. P.Gordo, I.2023-01-25T11:43:43Z2022-03-292022-03-29T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/8454engEvol Med Public Health. 2022 Mar 29;10(1):142-155. doi: 10.1093/emph/eoac010. eCollection 20222050-620110.1093/emph/eoac010info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:42:27Zoai:repositorio.insa.pt:10400.18/8454Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:42:53.832512Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution |
title |
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution |
spellingShingle |
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution Amicone, M. SARS-CoV-2 Experimental Evolution Mutation Rate Mutator Virus Adaptation Infecções Sistémicas e Zoonoses |
title_short |
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution |
title_full |
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution |
title_fullStr |
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution |
title_full_unstemmed |
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution |
title_sort |
Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution |
author |
Amicone, M. |
author_facet |
Amicone, M. Borges, V. Alves, M.J. Isidro, J. Zé-Zé, L. Duarte, S. Gomes, J. P. Gordo, I. |
author_role |
author |
author2 |
Borges, V. Alves, M.J. Isidro, J. Zé-Zé, L. Duarte, S. Gomes, J. P. Gordo, I. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Amicone, M. Borges, V. Alves, M.J. Isidro, J. Zé-Zé, L. Duarte, S. Gomes, J. P. Gordo, I. |
dc.subject.por.fl_str_mv |
SARS-CoV-2 Experimental Evolution Mutation Rate Mutator Virus Adaptation Infecções Sistémicas e Zoonoses |
topic |
SARS-CoV-2 Experimental Evolution Mutation Rate Mutator Virus Adaptation Infecções Sistémicas e Zoonoses |
description |
Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996265/ |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-03-29 2022-03-29T00:00:00Z 2023-01-25T11:43:43Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/8454 |
url |
http://hdl.handle.net/10400.18/8454 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Evol Med Public Health. 2022 Mar 29;10(1):142-155. doi: 10.1093/emph/eoac010. eCollection 2022 2050-6201 10.1093/emph/eoac010 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Oxford University Press/ on behalf of the Foundation for Evolution, Medicine, and Public Health |
publisher.none.fl_str_mv |
Oxford University Press/ on behalf of the Foundation for Evolution, Medicine, and Public Health |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132174796980224 |