Adaptation in outbred sexual yeast is repeatable, polygenic, and favors rare haplotypes

Abstract

We describe the results of a 200 generation Evolve and Resequence (E&R) study initiated from an outbred dipliod recombined synthetic base population derived from 18 genetically diverse founders. Replicate populations were maintained at large effective population sizes (>105 individuals), exposed to several different chemical challenges over 12 weeks of evolution, and whole-genome resequenced. Weekly forced outcrossing implies a per gene per cell-division recombination rate higher than that achieved in Drosophila E&R studies. In 55 sexual populations we observe large fitness gains and highly repeatable patterns of genome-wide haplotype change within each chemical challenge. There was little evidence for pervasive pleiotropy, as evidenced by patterns of haplotype change between drug treatments. Within treatment adaptation appears highly polygenic with almost the entire genome showing significant consistent haplotype change. Finally, adaptation was almost always associated with only one of the 18 founder alleles, suggesting selection primarily acts on rare variants private to a founder or haplotype blocks harboring multiple mutations. This observation contradicts the notion that adaptation is often due to subtle frequency shifts at intermediate frequency variants.