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 Saccharomycesspecies, S. cerevisiaeand 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. uvarumbut not the hybrid or S. cerevisiae. We find that S. uvarumalleles can be expressed at the same level as S. cerevisiaealleles 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. cerevisiaeand S. uvarumhas 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.

Keywords: Saccharomyces; allele-specific expression; cis-regulatory evolution; gene expression; interspecific hybrid; thermotolerance.

Fig. 1.—

Temperature dependent growth of Saccharomyces cerevisiae, S. uvarumand their hybrid. Growth is after 17 days at 4 °C, 3 days at 20 °C and 2 days at 33 °C and 37 °C, with platings on YPD at 1:3 serial dilutions.

Fig. 2.—

Temperature-dependent allele effects. The 136 genes with temperature-dependent allele effects are shown in color (legend) compared with all other genes (black, N = 4,919). (A) Species’ allele effects (Saccharomyces uvarum/S. cerevisiae) at low versus high temperature. (B) Temperature effects (37 °C/22 °C) of S. cerevisiae(Sc) versus S. uvarum(Su). Temperature effects are classified into those with species’ alleles have an opposite temperature response (red), the S. cerevisiaeallele responding to temperature more strongly than S. uvarum(green), and the S. uvarumallele responding to temperature more strongly than S. cerevisiae(blue).

Fig. 3.—

Temperature dependent HSP104expression in Saccharomyces cerevisiae, S. uvarumand their hybrid. Expression is based on qPCR with points showing the mean and bars the standard errors. Hybrid expression is the sum of the two alleles.