May 23, 2014

Precise estimates of mutation rate and spectrum in yeast

Proceedings of the National Academy of Sciences of the United States of America
Yuan O ZhuDmitri A Petrov

Abstract

Mutation is the ultimate source of genetic variation. The most direct and unbiased method of studying spontaneous mutations is via mutation accumulation (MA) lines. Until recently, MA experiments were limited by the cost of sequencing and thus provided us with small numbers of mutational events and therefore imprecise estimates of rates and patterns of mutation. We used whole-genome sequencing to identify nearly 1,000 spontaneous mutation events accumulated over ∼311,000 generations in 145 diploid MA lines of the budding yeast Saccharomyces cerevisiae. MA experiments are usually assumed to have negligible levels of selection, but even mild selection will remove strongly deleterious events. We take advantage of such patterns of selection and show that mutation classes such as indels and aneuploidies (especially monosomies) are proportionately much more likely to contribute mutations of large effect. We also provide conservative estimates of indel, aneuploidy, environment-dependent dominant lethal, and recessive lethal mutation rates. To our knowledge, for the first time in yeast MA data, we identified a sufficiently large number of single-nucleotide mutations to measure context-dependent mutation rates and were able to (i) confi...Continue Reading

  • References66
  • Citations136

References

  • References66
  • Citations136

Citations

Mentioned in this Paper

Genome-Wide Association Study
Noonan SYNDROME-LIKE Disorder With OR Without Juvenile Myelomonocytic Leukemia
Saccharomyces cerevisiae allergenic extract
Conidia
Cytosine Methylation
Natural Genetic Mutation
Aneuploid Cell
Genomics
Sequencing
Nucleotides

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