Loss-of-heterozygosity facilitates passage through Haldane's sieve for Saccharomyces cerevisiae undergoing adaptation.

Haldane's sieve posits that the majority of beneficial mutations that contribute to adaptation should be dominant, as these are the mutations most likely to establish and spread when rare. It has been argued, however, that if the dominance of mutations in their current and previous environments are correlated, Haldane's sieve could be eliminated. We constructed heterozygous lines of Saccharomyces cerevisiae containing single adaptive mutations obtained during exposure to the fungicide nystatin. Here we show that no clear dominance relationship exists across environments: mutations exhibited a range of dominance levels in a rich medium, yet were exclusively recessive under nystatin stress. Surprisingly, heterozygous replicates exhibited variable-onset rapid growth when exposed to nystatin. Targeted Sanger sequencing demonstrated that loss-of-heterozygosity (LOH) accounted for these growth patterns. Our experiments demonstrate that recessive beneficial mutations can avoid Haldane's sieve in clonal organisms through rapid LOH and thus contribute to rapid evolutionary adaptation.

Haploids adapt faster than diploids across a range of environments.

Despite a great deal of theoretical attention, we have limited empirical data about how ploidy influences the rate of adaptation. We evolved isogenic haploid and diploid populations of Saccharomyces cerevisiae for 200 generations in seven different environments. We measured the competitive fitness of all ancestral and evolved lines against a common competitor and find that in all seven environments, haploid lines adapted faster than diploids, significantly so in three environments. We apply theory that relates the rates of adaptation and measured effective population sizes to the properties of beneficial mutations. We obtained rough estimates of the average selection coefficients in haploids between 2% and 10% for these first selected mutations. Results were consistent with semi-dominant to dominant mutations in four environments and recessive to additive mutations in two other environments. These results are consistent with theory that predicts haploids should evolve faster than diploids at large population sizes.

Why have sex? The population genetics of sex and recombination.

One of the greatest puzzles in evolutionary biology is the high frequency of sexual reproduction and recombination. Given that individuals surviving to reproductive age have genomes that function in their current environment, why should they risk shuffling their genes with those of another individual? Mathematical models are especially important in developing predictions about when sex and recombination can evolve, because it is difficult to intuit the outcome of evolution with several interacting genes. Interestingly, theoretical analyses have shown that it is often quite difficult to identify conditions that favour the evolution of high rates of sex and recombination. For example, fitness interactions among genes (epistasis) can favour sex and recombination but only if such interactions are negative, relatively weak and not highly variable. One reason why an answer to the paradox of sex has been so elusive is that our models have focused unduly on populations that are infinite in size, unstructured and isolated from other species. Yet most verbal theories for sex and recombination consider a finite number of genotypes evolving in a biologically and/or physically complex world. Here, we review various hypotheses for why sex and recombination are so prevalent and discuss theoretical results indicating which of these hypotheses is most promising.