Independent evolution of transcript abundance and gene regulatory dynamics

Changes in gene expression drive novel phenotypes, raising interest in how gene expression evolves. Yet, comparative analysis of gene expression in related species have focused on few, equivalent conditions, providing little information about changes in the regulatory network controlling expression dynamics. To close this gap, we profiled the transcription response of related yeast species to hundreds of genetic and environmental perturbations. Consistent with previous reports, we observe massive variation in orthologous gene expression in each individual condition. By contrast, gene regulatory dynamics, quantified by co-expression analysis, remained largely conserved. Allele-specific profiling of inter-specific hybrid revealed that, while most variations in absolute expression result from gene-linked variations (cis effects), regulatory dynamics diverge mostly in trans. For example, lower expression of a transcription factor is linked with module switching of its targets, being nitrogen-repressed in one species but nitrogen-induced in the other. For certain transcription factors, we observe that mutations in binding sites are enriched in genes with altered dynamic pattern, rather than the expected reduction in expression levels, providing examples for rewiring in cis. Overall, our data suggests that gene expression diverges primarily by mutations that alter promoter strength, while maintaining dynamic regulatory properties largely intact.