Abstract
Through its fermentative capacities, Saccharomyces cerevisiae was central in the development of civilisation during the Neolithic period, and the yeast remains of importance in industry and biotechnology, giving rise to bona fide domesticated populations. Here, we conduct a population genomic study of domesticated and wild populations of S. cerevisiae . Using coalescent analyses, we report that the effective population size of yeast populations decreased since the divergence with S. paradoxus . We fitted models of distributions of fitness effects to infer the rate of adaptive () and non‐adaptive () non‐synonymous substitutions in protein‐coding genes. We report an overall limited contribution of positive selection to S. cerevisiae protein evolution, albeit with higher rates of adaptive evolution in wild compared to domesticated populations. Our analyses revealed the signature of background selection and possibly Hill–Robertson interference, as recombination was found to be negatively correlated with and positively correlated with . However, the effect of recombination on was found to be labile, as it is only apparent after removing the impact of codon usage bias on the synonymous site frequency spectrum and disappears if we control for the correlation with , suggesting that it could be an artefact of the decreasing population size. Furthermore, the rate of adaptive non‐synonymous substitutions is significantly correlated with the residue solvent exposure, a relation that cannot be explained by the population's demography. Together, our results provide a detailed characterisation of adaptive mutations in protein‐coding genes across S. cerevisiae populations.