The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus.
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.
Sanjuán
Rafael
R
Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de València, P.O. Box 22085, 46071 Valencia, Spain. rafael.sanjuan@uv.es
Moya
Andrés
A
Elena
Santiago F
SF
D000818:Animals; D005075:Biological Evolution; D014644:Genetic Variation; D005828:Genetics, Population; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*