Differential paralog divergence modulates genome evolution across yeast species

Abstract

Evolutionary outcomes depend not only on the selective forces acting upon a species, but also on the genetic background. However, large timescales and uncertain historical selection pressures can make it difficult to discern such important background differences between species. Experimental evolution is one tool to compare evolutionary potential of known genotypes in a controlled environment. Here we utilized a highly reproducible evolutionary adaptation in Saccharomyces cerevisiae to investigate whether experimental evolution of other yeast species would select for similar adaptive mutations. We evolved populations of S. cerevisiae, S. paradoxus, S. mikatae, S. uvarum, and interspecific hybrids between S. uvarum and S. cerevisiae for ~200–500 generations in sulfate-limited continuous culture. Wild-type S. cerevisiae cultures invariably amplify the high affinity sulfate transporter gene, SUL1. However, while amplification of the SUL1 locus was detected in S. paradoxus and S. mikatae populations, S. uvarum cultures instead selected for amplification of the paralog, SUL2. We measured the relative fitness of strains bearing deletions and amplifications of both SUL genes from different species, confirming that, converse to S. cerevisiae, S. uvarum SUL2 contributes more to fitness in sulfate limitation than S. uvarum SUL1. By measuring the fitness and gene expression of chimeric promoter-ORF constructs, we were able to delineate the cause of this differential fitness effect primarily to the promoter of S. uvarum SUL1. Our data show evidence of differential sub-functionalization among the sulfate transporters across Saccharomyces species through recent changes in noncoding sequence. Furthermore, these results show a clear example of how such background differences due to paralog divergence can drive changes in genome evolution.

Fitness Benefits of Loss of Heterozygosity in SaccharomycesHybrids

“…These strains have fitness benefits compared to the fully heterozygous ancestor strain. One strain containing two LOH regions was evolved in sulfate limitation, where adaptation is largely dominated by amplification of the SUL1 sulfate transporter gene (Brewer et al 2015;Sanchez et al 2017a). In this strain, we did not identify any single candidate gene deletions that had fitness benefits above our control strain cutoff of 0.046 in either region, consistent with this hypothesis.…”

“…In order to understand hybrid LOH, in this study we utilized two divergent species: S. cerevisiae and S. uvarum. We previously evolved hybrids and diploids of these species in nutrient-limited chemostat culture (Gresham et al 2008;Sanchez et al 2017a;Smukowski Heil et al 2017;2018b). We created thousands of S. cerevisiae x S. uvarum hybrid yeast strains by mating the S. cerevisiae nonessential deletion collection to WT S. uvarum.…”

Polymorphisms in the yeast galactose sensor underlie a natural continuum of nutrient-decision phenotypes

“…A number of labs have analyzed phenotypic variation in response to a range of environmental conditions [4,64,65] and delved into the genetic basis of variation in specific traits such as heat tolerance [66], gene/protein expression [67,68], sporulation efficiency [69-71], colony morphology [72-75], sulfur uptake [76], and carbon regulation [36,55]. The vast majority of these studies used growth or expression level [67] as readout.…”

Polymorphisms in the yeast galactose sensor underlie a natural continuum of nutrient-decision phenotypes

“…A number of labs have analyzed phenotypic variation in response to a range of environmental conditions [4,65,66] and delved into the genetic basis of variation in specific traits such as heat tolerance [67], gene/protein expression [68,69], sporulation efficiency [70–72], colony morphology [73–76], sulfur uptake [77], and carbon regulation [36,55]. The vast majority of these studies used growth or expression level [68] as readout.…”