Genetic mapping of experimental evolution in yeast

Understanding the molecular mechanisms by which organisms adapt to different environments is a fundamental question in evolutionary biology. Uncovering the genetic basis of evolutionary adaptation is limited by our ability to efficiently identify the genomic locations of adaptive mutations. We begin by describing a method based on linkage analysis, that can quickly and precisely map the genetic basis of naturally and experimentally evolved complex traits. A yeast strain that expresses the evolved trait is crossed to a distinct strain background and DNA from a large pool of progeny that express the trait of interest is hybridized to oligonucleotide microarrays that detect thousands of polymorphisms between the two strains. Adaptive mutations are detected by linkage to the polymorphisms from the evolved parent. We successfully tested our method by mapping five known genes to a precision of 0.2 to 24 kilobases (0.1 to 10 centimorgans), and developed computer simulations to test the effect of different factors on mapping precision. We then applied the mapping method to four yeast strains that had independently adapted to a fluctuating glucose-galactose environment. All four strains had acquired one or more missense mutations in GAL80, the repressor of the galactose utilization pathway. When transferred into the ancestral strain, the gal80 mutations conferred the fitness advantage that the evolved strains show in the transition from glucose to galactose. These results display an example of parallel adaptation caused by mutations in the same gene. Finally, we applied our method to an experimentally evolved complex trait---an intra-population mating preference.

We found 10 to 17 regions in the four strains that are linked to the mating preference or other traits that were inadvertently selected for during the evolution experiment, such as drug resistance. Considerable overlap was found between the linkage regions of all four evolved strains, suggesting parallel evolution at the genetic level also for the mating preference. Additional linkage analyses, sequencing and reconstruction experiments will be needed to find the adaptive mutations associated with the mating preference and confirm their contribution to the trait.