A comprehensive genotype-fitness map of adaptation-driving mutations in yeast

Adaptive evolution is a major driving force behind the phenotypic variation observed in nature, yet current methods are unsuitable for characterizing the molecular basis and fitness effects of large numbers of individual adaptive mutations. Here we have used a DNA barcoding approach to characterize the genotype-fitness map for adaptation-driving mutations in a Saccharomyces cerevisiae population experimentally evolving under glucose limitation. We isolated and measured the fitness of thousands of independently evolved adaptive clones in a highly parallel manner, and sequenced the whole genomes of hundreds of these adaptive clones. We have identified two major classes of adaptive mutations: self-diploidization, and mutations in the nutrient-responsive Ras/PKA and TOR/Sch9 pathways. Our large sample size and precision of measurement has allowed us to observe that within each pathway there are significant differences in fitness among mutations in different genes, different paralogs, and even for different classes of mutations within the same gene.