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The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus

AuthorsSanjuán, Rafael ; Moya-Simarro, Andrés; Elena, Santiago F.
KeywordsMutational fitness effects
RNA viral genomes
Single-nucleotide substitutions
Evolutionary biology
Issue Date24-May-2004
PublisherNational Academy of Sciences (U.S.)
CitationProc. Natl. Acad. Sci. USA 101(22): 8396-8401 (2004)
AbstractLittle is known about the mutational fitness effects associated with single-nucleotide substitutions on RNA viral genomes. Here, we used site-directed mutagenesis to create 91 single mutant clones of vesicular stomatitis virus derived from a common ancestral cDNA and performed competition experiments to measure the relative fitness of each mutant. The distribution of nonlethal deleterious effects was highly skewed and had a long, flat tail. As expected, fitness effects depended on whether mutations were chosen at random or reproduced previously described ones. The effect of random deleterious mutations was well described by a log-normal distribution, with -19% reduction of average fitness; the effects distribution of preobserved deleterious mutations was better explained by a β model. The fit of both models was improved when combined with a uniform distribution. Up to 40% of random mutations were lethal. The proportion of beneficial mutations was unexpectedly high. Beneficial effects followed a γ distribution, with expected fitness increases of 1% for random mutations and 5% for preobserved mutations.
Description6 pages, 3 figures.-- PMID: 15159545 [PubMed].-- PMCID: PMC420405.-- Supporting information (Table 3: Relevant information about each single-nucleotide substation mutant created) available at: http://www.pnas.org/content/101/22/8396/suppl/DC1
Printed version published on Jun 1, 2004.
Full-text paper available Open Access via PubMed Central: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15159545
Publisher version (URL)http://dx.doi.org/10.1073/pnas.0400146101
Appears in Collections:(IBMCP) Artículos
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