Loss of Heterozygosity Drives Adaptation in Hybrid Yeast

TLDR

Hybridization can enable invasion of new ecological niches, yet the genomic changes that facilitate adaptation after hybridization remain poorly understood. The study investigates hybrid genome evolution by experimentally evolving de novo interspecific hybrids of *Saccharomyces cerevisiae* × *S. uvarum* and their parentals. The authors performed experimental evolution in nutrient‑limited media for hundreds of generations, sequenced the evolved cultures to identify mutations, copy‑number changes, and loss‑of‑heterozygosity events, and used allele‑replacement assays to test the fitness effects of specific alleles.

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.