Loss of Heterozygosity Drives Adaptation in Hybrid Yeast

Abstract

Hybridization is often considered maladaptive, but sometimes hybrids can invade new ecological niches and adapt to novel or stressful environments better than their parents. The genomic changes that occur following hybridization that facilitate genome resolution and/or adaptation are not well understood. Here, we examine hybrid genome evolution using experimental evolution of de novo interspecific hybrid yeast Saccharomyces cerevisiae × Saccharomyces uvarum and their parentals. We evolved these strains in nutrient-limited conditions for hundreds of generations and sequenced the resulting cultures identifying numerous point mutations, copy number changes, and loss of heterozygosity (LOH) events, including species-biased amplification of nutrient transporters. We focused on a particularly interesting example, in which we saw repeated LOH at the high-affinity phosphate transporter gene PHO84 in both intra- and interspecific hybrids. Using allele replacement methods, we tested the fitness of different alleles in hybrid and S. cerevisiae strain backgrounds and found that the LOH is indeed the result of selection on one allele over the other in both S. cerevisiae and the hybrids. This is an example where hybrid genome resolution is driven by positive selection on existing heterozygosity and demonstrates that even infrequent outcrossing may have lasting impacts on adaptation.

Aneuploidy in yeast: Segregation error or adaptation mechanism?

“…Recently, a growing number of studies link aneuploidy to adaptation, suggesting that aneuploidy (as a result of nondisjunction during mitotic division) may provide a natural, but transient, route to rapid adaptive evolution in microbial populations (Chang, Lai, Tung, & Leu, ; Hose et al, ; Smukowski Heil et al, ). For instance, several experimental evolution studies using yeast (Chen, Bradford, Seidel, & Li, ; Gorter et al, ; Pavelka et al, ; Selmecki et al, ; Selmecki, Dulmage, Cowen, Anderson, & Berman, ; Yona et al, ) and other pathogenic fungi such as Candida albicans (Selmecki, Forche, & Berman, ) and Cryptococcus neoformans (Gerstein et al, ) suggest that aneuploidy can confer increased stress and drug resistance.…”

Yeast two‐ and three‐species hybrids and high‐sugar fermentation

“…gradually improves its fitness (e.g. Piotrowski et al, 2012;Dunn et al, 2013;Lopandic et al, 2016;Smukowski Heil et al, 2017;Krogerus et al, 2018). Where investigated, the improved fitness turned out to be associated with the accumulation of segregants ('evolved hybrids' or 'evolved variants') of specific types of chimeric genomes in the population.…”

Meeting Report on Experimental Approaches to Evolution and Ecology Using Yeast and Other Model Systems

“…Using experimental studies in chemostats, her lab found that hybrids repeatedly lose heterozygosity at genes that are amplified in the parental genomes and, at least for the examples studied, these events are the result of positive selection of one allele (Smukowski Heil et al 2017). The results imply that even infrequent outcrossing may have lasting impacts on adaptation.…”