<i>Cis</i>-regulatory variants affect gene expression dynamics in yeast.

Abstract

Evolution of <i>cis</i>-regulatory sequences depends on how they affect gene expression and motivates both the identification and prediction of <i>cis</i>-regulatory variants responsible for expression differences within and between species. While much progress has been made in relating <i>cis</i>-regulatory variants to expression levels, the timing of gene activation and repression may also be important to the evolution of <i>cis</i>-regulatory sequences. We investigated allele-specific expression (ASE) dynamics within and between <i>Saccharomyces</i> species during the diauxic shift and found appreciable <i>cis</i>-acting variation in gene expression dynamics. Within-species ASE is associated with intergenic variants, and ASE dynamics are more strongly associated with insertions and deletions than ASE levels. To refine these associations, we used a high-throughput reporter assay to test promoter regions and individual variants. Within the subset of regions that recapitulated endogenous expression, we identified and characterized <i>cis</i>-regulatory variants that affect expression dynamics. Between species, chimeric promoter regions generate novel patterns and indicate constraints on the evolution of gene expression dynamics. We conclude that changes in <i>cis</i>-regulatory sequences can tune gene expression dynamics and that the interplay between expression dynamics and other aspects of expression is relevant to the evolution of <i>cis</i>-regulatory sequences.