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Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8396-401. Epub 2004 May 24.

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

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1
Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de València, P.O. Box 22085, 46071 Valencia, Spain. rafael.sanjuan@uv.es

Abstract

Little 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 beta 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 gamma distribution, with expected fitness increases of 1% for random mutations and 5% for preobserved mutations.

PMID:
15159545
PMCID:
PMC420405
DOI:
10.1073/pnas.0400146101
[Indexed for MEDLINE]
Free PMC Article
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