Hitchhiking and epistasis give rise to cohort dynamics in adapting populations

ABSTRACT Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically-linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection, yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations. Here we utilize a bulk-segregant approach to identify the beneficial mutations across 11 lineages of experimentally-evolved yeast populations. We report that most genome sequence evolution is non-adaptive: nearly 80% of detected mutations have no discernable effects on fitness and less than 1% are deleterious. We determine the distribution of driver and hitchhiker mutations in 31 mutational cohorts, groups of up to ten mutations that arise synchronously from low frequency and track tightly with one another. Surprisingly, we find that one-third of cohorts lack identifiable driver mutations. In addition, we identify intra-cohort synergistic epistasis between mutations in hsl7 and kel1 , which arose together in a low frequency lineage.