The fitness effects of synonymous mutations in DNA and RNA viruses

Despite being silent with respect to protein sequence, synonymous nucleotide substitutions can be targeted by natural selection directly at the DNA or RNA level. However, there has been no systematic assessment of how frequent this type of selection is. Here, we have constructed 53 single random syn...

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Detalhes bibliográficos
Autores: Cuevas, José M., Domingo-Calap, Pilar, Sanjuán, Rafael
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2012
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/402166
Acesso em linha:http://hdl.handle.net/10261/402166
Access Level:Acceso aberto
Palavra-chave:Synonymous substitutions
Nonsynonymous substitutions
Silent substitutions
RNA structure
Codon usage bias
RNA virus
DNA virus
Mutational robustness
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spelling The fitness effects of synonymous mutations in DNA and RNA virusesCuevas, José M.Domingo-Calap, PilarSanjuán, RafaelSynonymous substitutionsNonsynonymous substitutionsSilent substitutionsRNA structureCodon usage biasRNA virusDNA virusMutational robustnessDespite being silent with respect to protein sequence, synonymous nucleotide substitutions can be targeted by natural selection directly at the DNA or RNA level. However, there has been no systematic assessment of how frequent this type of selection is. Here, we have constructed 53 single random synonymous substitution mutants of the bacteriophages Qβ and ΦX174 by site-directed mutagenesis and assayed their fitness. Analysis of this mutant collection and of previous studies undertaken with a variety of single-stranded (ss) viruses demonstrates that selection at synonymous sites is stronger in RNA viruses than in DNA viruses. We estimate that this type of selection contributes approximately 18% of the overall mutational fitness effects in ssRNA viruses under our assay conditions and that random synonymous substitutions have a 5% chance of being lethal to the virus, whereas in ssDNA viruses, these figures drop to 1.4% and 0%, respectively. In contrast, the effects of nonsynonymous substitutions appear to be similar in ssRNA and ssDNA viruses.This work was financially supported by grant BFU2008-03978/BMC and the Ramon y Cajal research program from the Spanish Ministerio de Ciencia e Innovacion (MICINN) to R.S., the Juan de la Cierva research program from MICINN to J.M.C., and a predoctoral fellowship from the Generalitat Valenciana to P.D.-C.Peer reviewedOxford University PressMinisterio de Ciencia e Innovación (España)Generalitat Valenciana202520252012info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/402166reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésCuevas, José M.; Domingo-Calap, Pilar; Sanjuán, Rafael; 2012; Supplementary data for The fitness effects of synonymous mutations in DNA and RNA viruses [Dataset]; Oxford University Press; https://doi.org/10.1093/molbev/msr179https://doi.org/10.1093/molbev/msr179Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4021662026-05-22T06:33:51Z
dc.title.none.fl_str_mv The fitness effects of synonymous mutations in DNA and RNA viruses
title The fitness effects of synonymous mutations in DNA and RNA viruses
spellingShingle The fitness effects of synonymous mutations in DNA and RNA viruses
Cuevas, José M.
Synonymous substitutions
Nonsynonymous substitutions
Silent substitutions
RNA structure
Codon usage bias
RNA virus
DNA virus
Mutational robustness
title_short The fitness effects of synonymous mutations in DNA and RNA viruses
title_full The fitness effects of synonymous mutations in DNA and RNA viruses
title_fullStr The fitness effects of synonymous mutations in DNA and RNA viruses
title_full_unstemmed The fitness effects of synonymous mutations in DNA and RNA viruses
title_sort The fitness effects of synonymous mutations in DNA and RNA viruses
dc.creator.none.fl_str_mv Cuevas, José M.
Domingo-Calap, Pilar
Sanjuán, Rafael
author Cuevas, José M.
author_facet Cuevas, José M.
Domingo-Calap, Pilar
Sanjuán, Rafael
author_role author
author2 Domingo-Calap, Pilar
Sanjuán, Rafael
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Generalitat Valenciana
dc.subject.none.fl_str_mv Synonymous substitutions
Nonsynonymous substitutions
Silent substitutions
RNA structure
Codon usage bias
RNA virus
DNA virus
Mutational robustness
topic Synonymous substitutions
Nonsynonymous substitutions
Silent substitutions
RNA structure
Codon usage bias
RNA virus
DNA virus
Mutational robustness
description Despite being silent with respect to protein sequence, synonymous nucleotide substitutions can be targeted by natural selection directly at the DNA or RNA level. However, there has been no systematic assessment of how frequent this type of selection is. Here, we have constructed 53 single random synonymous substitution mutants of the bacteriophages Qβ and ΦX174 by site-directed mutagenesis and assayed their fitness. Analysis of this mutant collection and of previous studies undertaken with a variety of single-stranded (ss) viruses demonstrates that selection at synonymous sites is stronger in RNA viruses than in DNA viruses. We estimate that this type of selection contributes approximately 18% of the overall mutational fitness effects in ssRNA viruses under our assay conditions and that random synonymous substitutions have a 5% chance of being lethal to the virus, whereas in ssDNA viruses, these figures drop to 1.4% and 0%, respectively. In contrast, the effects of nonsynonymous substitutions appear to be similar in ssRNA and ssDNA viruses.
publishDate 2012
dc.date.none.fl_str_mv 2012
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/402166
url http://hdl.handle.net/10261/402166
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cuevas, José M.; Domingo-Calap, Pilar; Sanjuán, Rafael; 2012; Supplementary data for The fitness effects of synonymous mutations in DNA and RNA viruses [Dataset]; Oxford University Press; https://doi.org/10.1093/molbev/msr179
https://doi.org/10.1093/molbev/msr179
No
dc.rights.none.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
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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