Fitness benefits of loss of heterozygosity in Saccharomyces hybrids

Abstract

With two genomes in the same organism, interspecific hybrids have unique fitness opportunities and costs. In both plants and yeasts, wild, pathogenic, and domesticated hybrids may eliminate portions of one parental genome, a phenomenon known as loss of heterozygosity (LOH). Laboratory evolution of hybrid yeast recapitulates these results, with LOH occurring in just a few hundred generations of propagation. In this study, we systematically looked for alleles that are beneficial when lost in order to determine how prevalent this mode of adaptation may be and to determine candidate loci that might underlie the benefits of larger-scale chromosome rearrangements. These aims were accomplished by mating Saccharomyces uvarum with the S. cerevisiae deletion collection to create hybrids such that each nonessential S. cerevisiae allele is deleted. Competitive fitness assays of these pooled, barcoded, hemizygous strains, and accompanying controls, revealed a large number of loci for which LOH is beneficial. We found that the fitness effects of hemizygosity are dependent on the species context, the selective environment, and the species origin of the deleted allele. Further, we found that hybrids have a wider distribution of fitness consequences versus matched S. cerevisiae hemizygous diploids. Our results suggest that LOH can be a successful strategy for adaptation of hybrids to new environments, and we identify candidate loci that drive the chromosomal rearrangements observed in evolution of yeast hybrids.

Figure 1.

Scatter plot of fitness values for hybrid and diploid S. cerevisiae strains hemizygous for deletion mutations, measured in glucose limitation (comparisons in other nutrient limitations can be found in Supplemental Fig. S4). Black strains fall inside the 1% cutoff in both axes, purple strains fall outside the 1% cutoff in just one axis, and the other colors fall outside of the cutoffs in both axes. Data from Supplemental Table S1. R² = 0.00.

Figure 2.

Fitness values of hybrids compared in glucose and phosphate limitation. Strains in black fall inside the 1% cutoff in both axes, purple strains fall outside the 1% cutoff in just one axis, and the other colors fall outside of the cutoffs in both axes. Comparisons between other media are shown in Supplemental Figure S5. Data from Supplemental Table S1. R² = 0.00.

Figure 3.

Reciprocal hemizygosity analysis correlation between S. cerevisiae deletion (x-axis) and S. uvarum deletion (y-axis). R² = 0.09, P = 0.25 (P-value for correlation). All nutrient environments included.