Fitness Benefits of Loss of Heterozygosity in SaccharomycesHybrids

Abstract

With two genomes in the same organism, interspecific hybrids have unique 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 larger distribution of fitness consequences vs. 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.

Loss of heterozygosity results in rapid but variable genome homogenization across yeast genetic backgrounds

“…The diploid organisms (or those with a higher ploidy) are usually heterozygous for many of these genetic variants across the genome. Nevertheless, a large number of studies have pointed out that regions of the genome can frequently become homozygous for these polymorphisms during mitotic divisions (7)(8)(9)(10)(11)(12)(13)(14)(15). These loss of heterozygosity (LOH) events result from the transfer of information from one homologous chromosome to the other, primarily a consequence of mitotic recombination, among other mechanisms (16).…”

Laboratory Evolution of a Saccharomyces cerevisiae × S. eubayanus Hybrid Under Simulated Lager-Brewing Conditions

“…Similarly, the superior growth of S. cerevisiae at 30°C relative to S. paradoxus could be linked to S. cerevisiae alleles of eight genes by investigating the effect of loss of heterozygosity in a laboratory hybrid (Weiss et al, 2018). Moreover, the deletion of S. cerevisiae alleles in S. uvarum × S. cerevisiae had strong and varying impacts on fitness under glucose-, sulfate- and phosphate-limitation (Lancaster et al, 2018). Overall, loss of heterozygosity is an irreversible process which enables rapid adaptation of hybrid genomes to the selective pressure of their growth environment.…”

Genome fractionation and loss of heterozygosity in hybrids and polyploids: mechanisms, consequences for selection, and link to gene function

“…Benefits of LOH in hybrids has been directly tested in only a few studies (Smukowski Heil et al 2017;Smukowski Heil et al 2019). Even in these cases, the benefits of LOH appeared quite complex and specific for a given allele, subgenome, and environmental conditions (Lancaster et al 2019). Although we could not directly examine the effects of LOH, our study revealed some parallel trends in LOH among independent hybrid strains.…”

“…However, the situation is likely more complex as orthologs may also be lost or retained for proper dosage of molecular interactors and relative copy number of their gene products, i.e., selection for stoichiometry (Birchler and Veitia 2012). Hybrid populations may also selectively filter orthologous genes according to their adaptive value in a given environment (Gittelman et al 2016;Lancaster et al 2019;Smukowski Heil et al 2019). Thus, despite the application of modern technologies, the question why some genes tend to be retained in heterozygous or duplicated states, whereas others are subjected to fractionation still represents a major evolutionary puzzle.…”

“…Such a gap in current knowledge partly results from taxonomic bias in knowledge, particularly toward plant species, as the incidence of hybridization and polyploidy have traditionally been underrated by zoologists. Moreover, direct tests for determining adaptive values of genomic rearrangements could be performed under laboratory conditions only, thereby focusing on rapidly reproducing organisms (Smukowski Heil et al 2017;Lancaster et al 2019) as events like LOH are rather rare (Dukić et al 2019). For practical reasons, most available data are derived from natural hybrids and polyploids, making it difficult to discern the patterns that are direct consequences of genome merging and those that evolved subsequently.…”