Abstract
Evolution of cis-regulatory sequences depends on how they affect gene expression and motivates both the identification and prediction of cis-regulatory variants responsible for expression differences within and between species. While much progress has been made in relating cis-regulatory variants to expression levels, the timing of gene activation and repression may also be important to the evolution of cis-regulatory sequences. We investigated allele-specific expression (ASE) dynamics within and between Saccharomyces species during the diauxic shift and found appreciable cis-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 cis-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 cis-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 cis-regulatory sequences.
Highlights
Noncoding cis-regulatory sequences control gene expression and are thought to play a central role in evolution (Carroll, 2005)
Hybrids were generated by crossing a North American Saccharomyces cerevisiae strain (Oak) to an S. cerevisiae wine strain (Wine) and two strains from China (China I and China II), as well as to a strain of Saccharomyces paradoxus and Saccharomyces uvarum (Table S1 in Supplementary file 1), enabling us to examine a range of divergence in gene regulation
We find that while gene expression dynamics are interrelated to expression levels, they differ in the types and identities of variants perturbing them
Summary
Noncoding cis-regulatory sequences control gene expression and are thought to play a central role in evolution (Carroll, 2005). In the case of orthologous genes from different species, binding site turnover and transcription factor re-wiring explain substantial divergence in cis-regulatory sequences without expression divergence Predicting changes in gene expression based on variation in individual transcription factor binding sites has proven difficult (Doniger and Fay, 2007; Doniger et al, 2008). Over a third of yeast intergenic sequences are estimated to be under selective constraint (Chin et al, 2005; Doniger et al, 2005) This fraction is greater than that expected from either conserved or experimentally identified binding sites (Doniger et al, 2005; Venkataram and Fay, 2010). Our results inform our understanding of variation in gene expression dynamics and point towards an integrated view of gene expression and how it evolves
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