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

Detalhes bibliográficos
Autor(a) principal: Amicone, M.
Data de Publicação: 2022
Outros Autores: Borges, V., Alves, M.J., Isidro, J., Zé-Zé, L., Duarte, S., Gomes, J. P., Gordo, I.
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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spelling 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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