Spontaneous Polyploids and Antimutators Compete During the Evolution of Saccharomyces cerevisiae Mutator Cells.

Genetics
Maxwell TracyAlan J Herr

Abstract

Mutations affecting DNA polymerase exonuclease domains or mismatch repair (MMR) generate "mutator" phenotypes capable of driving tumorigenesis. Cancers with both defects exhibit an explosive increase in mutation burden that appears to reach a threshold, consistent with selection acting against further mutation accumulation. In Saccharomyces cerevisiae haploid yeast, simultaneous defects in polymerase proofreading and MMR select for "antimutator" mutants that suppress the mutator phenotype. We report here that spontaneous polyploids also escape this "error-induced extinction" and routinely outcompete antimutators in evolved haploid cultures. We performed similar experiments to explore how diploid yeast adapt to the mutator phenotype. We first evolved cells with homozygous mutations affecting polymerase δ proofreading and MMR, which we anticipated would favor tetraploid emergence. While tetraploids arose with a low frequency, in most cultures, a single antimutator clone rose to prominence carrying biallelic mutations affecting the polymerase mutator alleles. Variation in mutation rate between subclones from the same culture suggests that there exists continued selection pressure for additional antimutator alleles. We then evolved...Continue Reading

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Citations

Dec 4, 2020·Genetics·Linda J Reha-Krantz, Myron F Goodman
Jan 28, 2021·FEMS Microbiology Reviews·Aleeza C Gerstein, Nathaniel P Sharp
Mar 26, 2021·Nucleic Acids Research·Mareike HerzogFabio Puddu
May 7, 2021·Genetics·Linda J Reha-Krantz, Myron F Goodman

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