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Genetics. Jan 2001; 157(1): 53–61.
PMCID: PMC1461475

Estimates of the rate and distribution of fitness effects of spontaneous mutation in Saccharomyces cerevisiae.


The per-genome, per-generation rate of spontaneous mutation affecting fitness (U) and the mean fitness cost per mutation (s) are important parameters in evolutionary genetics, but have been estimated for few species. We estimated U and sh (the heterozygous effect of mutations) for two diploid yeast strains differing only in the DNA mismatch-repair deficiency used to elevate the mutation rate in one (mutator) strain. Mutations were allowed to accumulate in 50 replicate lines of each strain, during 36 transfers of randomly chosen single colonies (approximately 600 generations). Among wild-type lines, fitnesses were bimodal, with one mode showing no change in mean fitness. The other mode showed a mean 29.6% fitness decline and the petite phenotype, usually caused by partial deletion of the mitochondrial genome. Excluding petites, maximum-likelihood estimates adjusted for the effect of selection were U = 9.5 x 10(-5) and sh = 0.217 for the wild type. Among the mutator lines, the best fit was obtained with 0.005 < or = U < or = 0.94 and 0.049 > or = sh > or = 0.0003. Like other recently tested model organisms, wild-type yeast have low mutation rates, with high mean fitness costs per mutation. Inactivation of mismatch repair increases the frequency of slightly deleterious mutations by approximately two orders of magnitude.

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Selected References

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  • Fernández J, López-Fanjul C. Spontaneous mutational variances and covariances for fitness-related traits in Drosophila melanogaster. Genetics. 1996 Jun;143(2):829–837. [PMC free article] [PubMed]
  • Fry JD, Keightley PD, Heinsohn SL, Nuzhdin SV. New estimates of the rates and effects of mildly deleterious mutation in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):574–579. [PMC free article] [PubMed]
  • García-Dorado A, López-Fanjul C, Caballero A. Properties of spontaneous mutations affecting quantitative traits. Genet Res. 1999 Dec;74(3):341–350. [PubMed]
  • Goebl MG, Petes TD. Most of the yeast genomic sequences are not essential for cell growth and division. Cell. 1986 Sep 26;46(7):983–992. [PubMed]
  • Hampsey M. A review of phenotypes in Saccharomyces cerevisiae. Yeast. 1997 Sep 30;13(12):1099–1133. [PubMed]
  • Keightley PD. The distribution of mutation effects on viability in Drosophila melanogaster. Genetics. 1994 Dec;138(4):1315–1322. [PMC free article] [PubMed]
  • Keightley PD. Nature of deleterious mutation load in Drosophila. Genetics. 1996 Dec;144(4):1993–1999. [PMC free article] [PubMed]
  • Keightley PD. Inference of genome-wide mutation rates and distributions of mutation effects for fitness traits: a simulation study. Genetics. 1998 Nov;150(3):1283–1293. [PMC free article] [PubMed]
  • Keightley PD, Caballero A. Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3823–3827. [PMC free article] [PubMed]
  • Keightley PD, Eyre-Walker A. Terumi Mukai and the riddle of deleterious mutation rates. Genetics. 1999 Oct;153(2):515–523. [PMC free article] [PubMed]
  • Kibota TT, Lynch M. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature. 1996 Jun 20;381(6584):694–696. [PubMed]
  • Kondrashov AS. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. [PubMed]
  • Kondrashov AS. Measuring spontaneous deleterious mutation process. Genetica. 1998;102-103(1-6):183–197. [PubMed]
  • Kondrashov AS, Houle D. Genotype-environment interactions and the estimation of the genomic mutation rate in Drosophila melanogaster. Proc Biol Sci. 1994 Dec 22;258(1353):221–227. [PubMed]
  • Korona R. Unpredictable fitness transitions between haploid and diploid strains of the genetically loaded yeast Saccharomyces cerevisiae. Genetics. 1999 Jan;151(1):77–85. [PMC free article] [PubMed]
  • Brown PA, Szostak JW. Yeast vectors with negative selection. Methods Enzymol. 1983;101:278–290. [PubMed]
  • Burns N, Grimwade B, Ross-Macdonald PB, Choi EY, Finberg K, Roeder GS, Snyder M. Large-scale analysis of gene expression, protein localization, and gene disruption in Saccharomyces cerevisiae. Genes Dev. 1994 May 1;8(9):1087–1105. [PubMed]
  • Marsischky GT, Filosi N, Kane MF, Kolodner R. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev. 1996 Feb 15;10(4):407–420. [PubMed]
  • Caballero A, Keightley PD. Inferences on genome-wide deleterious mutation rates in inbred populations of Drosophila and mice. Genetica. 1998;102-103(1-6):229–239. [PubMed]
  • Mukai T, Chigusa SI, Mettler LE, Crow JF. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics. 1972 Oct;72(2):335–355. [PMC free article] [PubMed]
  • Ohnishi O. Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. II. Homozygous effect of polygenic mutations. Genetics. 1977 Nov;87(3):529–545. [PMC free article] [PubMed]
  • Davies EK, Peters AD, Keightley PD. High frequency of cryptic deleterious mutations in Caenorhabditis elegans. Science. 1999 Sep 10;285(5434):1748–1751. [PubMed]
  • Arjan JA, Visser M, Zeyl CW, Gerrish PJ, Blanchard JL, Lenski RE. Diminishing returns from mutation supply rate in asexual populations. Science. 1999 Jan 15;283(5400):404–406. [PubMed]
  • Schultz ST, Lynch M, Willis JH. Spontaneous deleterious mutation in Arabidopsis thaliana. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11393–11398. [PMC free article] [PubMed]
  • Simmons MJ, Crow JF. Mutations affecting fitness in Drosophila populations. Annu Rev Genet. 1977;11:49–78. [PubMed]
  • Sniegowski PD, Gerrish PJ, Lenski RE. Evolution of high mutation rates in experimental populations of E. coli. Nature. 1997 Jun 12;387(6634):703–705. [PubMed]
  • Thatcher JW, Shaw JM, Dickinson WJ. Marginal fitness contributions of nonessential genes in yeast. Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):253–257. [PMC free article] [PubMed]
  • Zeyl C. Budding yeast as a model organism for population genetics. Yeast. 2000 Jun 15;16(8):773–784. [PubMed]
  • Vassilieva LL, Lynch M. The rate of spontaneous mutation for life-history traits in Caenorhabditis elegans. Genetics. 1999 Jan;151(1):119–129. [PMC free article] [PubMed]

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