Mutational effects depend on ploidy level: all else is not equal

Abstract

Ploidy is predicted to influence adaptation directly, yet whether single mutations behave the same in different ploidy backgrounds has not been well studied. It has often been assumed theoretically that aside from dominance, selective parameters do not differ between cells of varying ploidy. Using the budding yeast Saccharomyces cerevisiae, I compared the effect size of 20 adaptive mutations in haploids and homozygous diploids and found, surprisingly, that the same mutations often had a much larger effect in haploids than homozygous diploids. This empirical result demonstrates that it cannot be assumed that mutations will have the same effect in haploids and homozygous diploids.

Loss-of-heterozygosity facilitates passage through Haldane’s sieve for Saccharomyces cerevisiae undergoing adaptation

“…We hypothesize that the lower levels of nystatin permitted greater survival or growth, increasing the chance than an LOH event arose. This explanation is consistent with the lower number of ERG5 replicates that grew compared to other genes (43% of ERG5 replicates compared to 88%, 73% and 81% of ERG7, ERG6, and ERG3 replicates, respectively), as the ERG5 mutant line, BMN35, has a much reduced fitness in nystatin relative to other mutations 19 . Surprisingly, poor growth of the heterozygous lines was observed (except in lines that underwent LOH) even in 1 mM nystatin, a level of stressor in which the wild type was generally able to grow (Fig.…”

“…The mutations were acquired in background BY4741, MATa his3D1 leu2D0 met15D0 ura3D0, derived from S288c, which is considered to be 'wild type' with respect to mutation and recombination rates. To create heterozygous MATa/MATa diploids, we utilized the same method previously described to create MATa/MATa homozygous diploids 19 (heterozygous and homozygous lines were created at the same time). We transformed a single colony from each mutation line with plasmid pB2647 containing LEU2 while an ancestral BY4741colony was transformed with plasmid pB2649 containing URA3 and MATa (plasmids kindly donated by Dr David Pellman, Harvard Medical School).…”

“…Each line carries a mutation (identified through whole-genome sequencing) in one of four genes that act late in the ergosterol biosynthesis pathway (one mutation each in ERG7 and ERG5, seven unique mutations in ERG6 and eleven unique mutations in ERG3). These mutations confer a large fitness benefit in both haploids 18 and homozygous diploids 19 grown under nystatin stress, and yet bear a fitness cost relative to wild type in YPD (a rich medium composed of yeast extract, peptone and dextrose) 18 . Although the exact ecological history of the strain is unknown, YPD is a commonly used rich medium and we use it to represent a previously experienced and unstressful environment, relative to the novel and stressful environment containing nystatin.…”

As it happens: current directions in experimental evolution

“…Multiple contributions (the papers of Gerstein [10], Lalić & Elena [13], Matsuba et al [8] and Wang et al [12]) illustrate the way in which experimental evolution facilitates isolation and decisive testing of the effects of individual factors on evolution in replicate populations. In general, experimental evolution is moving towards ever-tighter integration of empirical data and theory, and this trend is well represented by the work of Gifford et al [17] and the theoretical contribution of Gordo & Campos [20] inspired by data from long-term evolution experiments.…”

“…Theoretical studies on these questions have typically assumed that beneficial mutations have identical effects in haploids and diploidsfor example, that a beneficial mutation in a haploid has the same fitness effect when homozygous in a diploid. Gerstein [10] uses a set of known beneficial mutations in the yeast Saccharomyces cerevisiae to test this assumption, with quite surprising results: beneficial mutations placed in haploids provide higher fitness benefits than the same mutations made homozygous in isogenic diploids. In Gerstein's experimental system, at least, all else is not equal in haploids and diploids.…”