Cis -regulatory divergence in gene expression between two thermally divergent yeast species

Abstract Gene regulation is a ubiquitous mechanism by which organisms respond to their environment. While organisms are often found to be adapted to the environments they experience, the role of gene regulation in environmental adaptation is not often known. In this study, we examine divergence in cis -regulatory effects between two Saccharomyces species, S. cerevisiae and S. uvarum , that have substantially diverged in their thermal growth profile. We measured allele specific expression (ASE) in the species’ hybrid at three temperatures, the highest of which is lethal to S. uvarum but not the hybrid or S. cerevisiae . We find that S. uvarum alleles can be expressed at the same level as S. cerevisiae alleles at high temperature and most cis -acting differences in gene expression are not dependent on temperature. While a small set of 136 genes show temperature-dependent ASE, we find no indication that signatures of directional cis -regulatory evolution are associated with temperature. Within promoter regions we find binding sites enriched upstream of temperature responsive genes, but only weak correlations between binding site and expression divergence. Our results indicate that temperature divergence between S. cerevisiae and S. uvarum has not caused widespread divergence in cis -regulatory activity, but point to a small subset of genes where the species’ alleles show differences in magnitude or opposite responses to temperature. The difficulty of explaining divergence in cis -regulatory sequences with models of transcription factor binding sites and nucleosome positioning highlights the importance of identifying mutations that underlie cis -regulatory divergence between species.