Adaptation in Outbred Sexual Yeast is Repeatable, Polygenic and Favors Rare Haplotypes

Abstract

We carried out a 200 generation Evolve and Resequence (E&R) experiment initiated from an outbred diploid recombined 18-way synthetic base population. Replicate populations were evolved 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 resulted in an average between adjacent-gene per cell division recombination rate of ∼0.0008. Despite attempts to force weekly sex, roughly half of our populations evolved cheaters and appear to be evolving asexually. Focusing on seven chemical stressors and 55 total evolved populations that remained sexual we observed large fitness gains and highly repeatable patterns of genome-wide haplotype change within chemical challenges, with limited levels of repeatability across chemical treatments. Adaptation appears highly polygenic with almost the entire genome showing significant and consistent patterns of haplotype change with little evidence for long range linkage disequilibrium in a subset of populations for which we sequenced haploid clones. That is, almost the entire genome is under selection or drafting with selected sites. At any given locus adaptation was almost always dominated by one of the 18 founder’s alleles, with that allele varying spatially and between treatments, suggesting that selection acts primarily on rare variants private to a founder or haplotype blocks harboring multiple mutations.

Strength of selection potentiates distinct adaptive responses in an evolution experiment with outcrossing yeast

“…On the issue of shared adaptation to laboratory conditions, it is worth noting that such responses are not readily observed in similar work from Linder et al (2022). Here the authors, also working with outcrossing yeast, characterize adaptation to different chemical stress treatments.…”

“…While some studies report high levels of evolutionary repeatability, as evidenced by parallel responses to selection across replicate populations (e.g. Linder et al 2022), others find more idiosyncratic and replicate-specific responses (e.g. Barghi et al 2019).…”

Embracing Complexity: Yeast Evolution Experiments Featuring Standing Genetic Variation

“…Significant computational resources accompany the biological resources, including software to map haplotype frequencies in any evolved populations derived from the 18X. In evolution experiments with standing genetic variation, tracking haplotype frequencies in addition to SNP frequencies has been shown to increase the power to identify genomic regions underlying adaptive change (e.g., Burke et al 2014 ; Linder et al 2022 ), as well as to distinguish between models of adaptation (Barghi and Schlötterer 2020 ). So, it is best practice to design any such experiment so that observed standing variation can be resolved back to the founder genotypes, whether one’s goal is to map individual traits or to analyze adaptive dynamics.…”

“…To give an illustrative example of how this practice can improve trait mapping, Wing et al ( 2020 ) showed that the signature of adaptive change in an evolution experiment for freeze–thaw tolerance was associated with a single genomic region; in this case a wild North American soil isolate was the only one of the four founders bearing the adaptive haplotype. To give an illustrative example of how this practice improves studies of adaptive dynamics, Linder et al ( 2022 ) showed that across a range of selective environments, adaptation was almost always associated with only one of the 18 founder genotypes, suggesting that selection tends to favor rare haplotypes.…”

“…An essential feature of any population one might use to start an evolution experiment with standing variation—whether it be one of the aforementioned resources or a newly synthesized population—is the ability to confirm and track successful mating events. Prior experiments have either used (i) strains engineered such that the different mating types have different auxotrophies, meaning that mated diploids can be recovered in dropout media (e.g., Parts et al 2011 , Burke et al 2014 , Vasquez-Garcia et al 2017 , Li et al 2019 ) or (ii) strains engineered such that the different mating types express different drug resistance cassettes, and mated diploids can be recovered in media supplemented with multiple antifungal drugs (e.g., Macdonald et al 2016 , Kolsheleva and Desai 2018 , Leu et al 2020 ; Linder et al 2022 ; Phillips et al 2022 ). In either case, haploid strains should first be heterothallic, with the HO gene knocked out.…”