title: A Genetic Incompatibility Accelerates Adaptation in Yeast.
abstract: During mismatch repair (MMR) MSH proteins bind to mismatches that form as the result of DNA replication errors and recruit MLH factors such as Mlh1-Pms1 to initiate excision and repair steps. Previously, we identified a negative epistatic interaction involving naturally occurring polymorphisms in the MLH1 and PMS1 genes of baker's yeast. Here we hypothesize that a mutagenic state resulting from this negative epistatic interaction increases the likelihood of obtaining beneficial mutations that can promote adaptation to stress conditions. We tested this by stressing yeast strains bearing mutagenic (incompatible) and non-mutagenic (compatible) mismatch repair genotypes. Our data show that incompatible populations adapted more rapidly and without an apparent fitness cost to high salt stress. The fitness advantage of incompatible populations was rapid but disappeared over time. The fitness gains in both compatible and incompatible strains were due primarily to mutations in PMR1 that appeared earlier in incompatible evolving populations. These data demonstrate a rapid and reversible role (by mating) for genetic incompatibilities in accelerating adaptation in eukaryotes. They also provide an approach to link experimental studies to observational population genomics.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Duyen T
authors.initials: DT
authors.lastname: Bui
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Elliot
authors.initials: E
authors.lastname: Dine
authors.affiliation: Department of Biology, University of Toronto, Mississauga, Ontario, Canada.
authors.forename: James B
authors.initials: JB
authors.lastname: Anderson
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Aquadro
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Alani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D018832:Molecular Chaperones; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D009997:Osmotic Pressure / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D055049:Salt Tolerance / Q000235:genetics*; D012965:Sodium Chloride / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C088859:MLH1 protein, S cerevisiae; D018832:Molecular Chaperones; C088858:PMS1 protein, S cerevisiae; C101767:SSC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012965:Sodium Chloride; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D000252:Calcium-Transporting ATPases