Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae

Abstract

We carried out a population genomic survey of Saccharomyces cerevisiae diploid isolates and find that many budding yeast strains have high levels of genomic heterozygosity, much of which is likely due to outcrossing. We demonstrate that variation in heterozygosity among strains is correlated with a life-history tradeoff that involves how readily yeast switch from asexual to sexual reproduction under nutrient stress. This trade-off is reflected in a negative relationship between sporulation efficiency and pseudohyphal development and correlates with variation in the expression of RME1, a transcription factor with pleiotropic effects on meiosis and filamentous growth. Selection for alternate lifehistory strategies in natural versus human-associated environments likely contributes to differential maintenance of genomic heterozygosity through its effect on the frequency that yeast lineages experience sexual cycles and hence the opportunity for inbreeding. In addition to elevated levels of heterozygosity, many strains exhibit large genomic regions of loss-of-heterozygosity (LOH), suggesting that mitotic recombination has a significant impact on genetic variation in this species. This study provides new insights into the roles that both outcrossing and mitotic recombination play in shaping the genome architecture of Saccharomyces cerevisiae. This study also provides a unique case where stark differences in the genomic distribution of genetic variation among individuals of the same species can be largely explained by a lifehistory trade-off.T he frequency of sex and the nature of breeding systems have a profound effect on genome variation and evolution. For example, inbred populations have an increased frequency of homozygous genotypes (1), lower effective rates of recombination (2), and smaller effective population sizes relative to outcrossed populations with the same number of individuals (3). Likewise, clonal populations are expected to exhibit high levels of heterozygosity coupled with increased allelic diversity but decreased genotypic diversity relative to sexual populations (4).The budding yeast Saccharomyces cerevisiae is one of the best studied model organisms, but relatively little is known about the importance of sexual versus asexual reproduction and inbreeding versus outcrossing in shaping genome evolution in this species. One recent study estimated that outcrossing occurs approximately once every 50,000 generations in S. cerevisiae (5), but low rates of outcrossing do not preclude the possibility that outcrossing has an important impact on genetic variation. Studies of the closely related yeast Saccharomyces paradoxus suggest that sexual cycles are rare relative to asexual cycles and that when sex does occur it primarily involves inbreeding (6, 7). However, S. paradoxus exhibits distinctly different intra-and interpopulation patterns of variation than does S. cerevisiae (8), and hence these findings may not be generalizable across the Saccharomyces genus.Patterns of heterozygosity are an important indica...

Effect of Domestication on the Spread of the [PIN+] Prion in Saccharomyces cerevisiae

“…While we found trends in mating and multicellular growth within clades, the diverse array of phenotypes observed in wild and domesticated isolates likely reflects the plasticity of this species in response to stress and habitat variability (Kvitek et al 2008;Liti et al 2009). In agreement with Magwene et al (2011), about half of our sampled isolates showed a preference for either asexual or sexual reproduction; however, the other half readily switched between sexual and asexual growth when exposed to different growth media. Phenotypic plasticity can be an advantage for yeast living in habitats where resources or growth conditions fluctuate (Halme et al 2004;Avery 2006;Bishop et al 2007;Yvert et al 2013).…”

“…Like ancient, wild strains of S. cerevisiae sampled in primeval forests of China (Wang et al 2012), isolates from the ancestral clade showed the highest levels of inbreeding and reproductive isolation. Furthermore, strains from this clade had sporulation efficiencies that were similar to wild, undomesticated isolates sampled in forests and much higher than most domesticated isolates (Gerke et al 2006;Magwene et al 2011;Wang et al 2012). Of course, sporulation is not sufficient to ensure frequent outcross mating.…”

“…Magwene et al (2011) suggested that artificial selection in some yeast lineages has favored asexual growth over sporulation. Indeed, strains in the wine clade generally showed poor sporulation and a greater tendency for pseudohyphal growth than most strains.…”

“…Ecological factors could influence mating frequency and thus prion prevalence in the wild. Magwene et al (2011) reported that strains from natural environments more readily undergo meiosis (under the tested conditions) compared to domesticated strains, whereas pseudohyphal growth was more readily induced in domesticated strains (Magwene et al 2011 Alternative to sporulation, nutrient deprivation can induce the formation of pseudohyphal filaments that allow yeast to invade solid media and forage for nutrients. This phenotype is highly variable, however, and even among genetically homogeneous strains only a subset of cells will undergo a pseudohyphal response to nutrient deprivation (Gimeno et al 1992).…”

The 100-genomes strains, an S. cerevisiae resource that illuminates its natural phenotypic and genotypic variation and emergence as an opportunistic pathogen

“…First, clinically derived strains comprised 59% of the mosaic strains (P = 0.00233, Fisher's exact test). Clinical S. cerevisiae isolates tend to be multiply heterozygous (Muller and McCusker 2009a;Magwene et al 2011), consistent with outcrossing between different S. cerevisiae populations and the clinical origin-mosaic group association. Similarly, in the human pathogens Toxoplasma gondii and Cryptococcus gattii, outcrossing between different populations results in progeny with mosaic genomes that have increased transmission, dissemination, and/or virulence phenotypes (Grigg and Suzuki 2003;Minot et al 2012;Voelz et al 2013).…”