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Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains.

Publication ,  Journal Article
Skelly, DA; Magwene, PM; Meeks, B; Murphy, HA
Published in: Proceedings. Biological sciences
April 2017

Natural selection has the potential to act on all phenotypes, including genomic mutation rate. Classic evolutionary theory predicts that in asexual populations, mutator alleles, which cause high mutation rates, can fix due to linkage with beneficial mutations. This phenomenon has been demonstrated experimentally and may explain the frequency of mutators found in bacterial pathogens. By contrast, in sexual populations, recombination decouples mutator alleles from beneficial mutations, preventing mutator fixation. In the facultatively sexual yeast Saccharomyces cerevisiae, segregating alleles of MLH1 and PMS1 have been shown to be incompatible, causing a high mutation rate when combined. These alleles had never been found together naturally, but were recently discovered in a cluster of clinical isolates. Here we report that the incompatible mutator allele combination only marginally elevates mutation rate in these clinical strains. Genomic and phylogenetic analyses provide no evidence of a historically elevated mutation rate. We conclude that the effect of the mutator alleles is dampened by background genetic modifiers. Thus, the relationship between mutation rate and microbial pathogenicity may be more complex than once thought. Our findings provide rare observational evidence that supports evolutionary theory suggesting that sexual organisms are unlikely to harbour alleles that increase their genomic mutation rate.

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Published In

Proceedings. Biological sciences

DOI

EISSN

1471-2954

ISSN

0962-8452

Publication Date

April 2017

Volume

284

Issue

1852

Start / End Page

20162672

Related Subject Headings

  • Selection, Genetic
  • Saccharomyces cerevisiae
  • Phylogeny
  • Mutation Rate
  • Mutation
  • Evolution, Molecular
  • Alleles
  • 41 Environmental sciences
  • 31 Biological sciences
  • 30 Agricultural, veterinary and food sciences
 

Citation

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Skelly, D. A., Magwene, P. M., Meeks, B., & Murphy, H. A. (2017). Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains. Proceedings. Biological Sciences, 284(1852), 20162672. https://doi.org/10.1098/rspb.2016.2672
Skelly, Daniel A., Paul M. Magwene, Brianna Meeks, and Helen A. Murphy. “Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains.Proceedings. Biological Sciences 284, no. 1852 (April 2017): 20162672. https://doi.org/10.1098/rspb.2016.2672.
Skelly DA, Magwene PM, Meeks B, Murphy HA. Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains. Proceedings Biological sciences. 2017 Apr;284(1852):20162672.
Skelly, Daniel A., et al. “Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains.Proceedings. Biological Sciences, vol. 284, no. 1852, Apr. 2017, p. 20162672. Epmc, doi:10.1098/rspb.2016.2672.
Skelly DA, Magwene PM, Meeks B, Murphy HA. Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains. Proceedings Biological sciences. 2017 Apr;284(1852):20162672.
Journal cover image

Published In

Proceedings. Biological sciences

DOI

EISSN

1471-2954

ISSN

0962-8452

Publication Date

April 2017

Volume

284

Issue

1852

Start / End Page

20162672

Related Subject Headings

  • Selection, Genetic
  • Saccharomyces cerevisiae
  • Phylogeny
  • Mutation Rate
  • Mutation
  • Evolution, Molecular
  • Alleles
  • 41 Environmental sciences
  • 31 Biological sciences
  • 30 Agricultural, veterinary and food sciences