6533b836fe1ef96bd12a14af
RESEARCH PRODUCT
The fitness effects of synonymous mutations in DNA and RNA viruses.
José M. CuevasRafael SanjuánPilar Domingo-calapsubject
Nonsynonymous substitutionvirusesBiologymedicine.disease_causeVirusKa/Ks ratioEvolution Molecularchemistry.chemical_compoundGeneticsmedicineRNA VirusesBacteriophagesSelection GeneticCodonMolecular BiologyEcology Evolution Behavior and SystematicsGeneticsMutationNatural selectionModels GeneticDNA VirusesRNAVirologychemistryMutationMutagenesis Site-DirectedGenetic FitnessSynonymous substitutionDNAdescription
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 Qb and UX174 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-07-21 | Molecular biology and evolution |