PT - JOURNAL ARTICLE AU - Katya L. Mack AU - Tyler A. Square AU - Bin Zhao AU - Craig T. Miller AU - Hunter B. Fraser TI - Evolution of spatial and temporal <em>cis</em>-regulatory divergence between marine and freshwater sticklebacks AID - 10.1101/2022.09.30.510353 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.09.30.510353 4099 - http://biorxiv.org/content/early/2022/10/01/2022.09.30.510353.short 4100 - http://biorxiv.org/content/early/2022/10/01/2022.09.30.510353.full AB - Cis-regulatory changes are thought to play a major role in adaptation. Threespine sticklebacks have repeatedly colonized freshwater habitats in the Northern Hemisphere, where they have evolved a suite of phenotypes that distinguish them from marine populations, including changes in physiology, behavior, and morphology. To understand the role of gene regulatory evolution in adaptive divergence, here we investigate cis-regulatory changes in gene expression between marine and freshwater ecotypes through allele-specific expression (ASE) in F1 hybrids. Surveying seven ecologically relevant tissues, including three sampled across two developmental stages, we identified cis-regulatory divergence affecting a third of genes, nearly half of which were tissue-specific. Next, we compared allele-specific expression in dental tissues at two timepoints to characterize cis-regulatory changes during development between marine and freshwater fish. Applying a genome-wide test for selection on cis-regulatory changes, we find evidence for lineage-specific selection on several processes, including the Wnt signaling pathway in dental tissues. Finally, we show that genes with ASE, particularly those that are tissue-specific, are enriched in genomic regions associated with marine-freshwater divergence, supporting an important role for cis-regulatory differences in adaptive evolution of sticklebacks. Altogether, our results provide insight into the cis-regulatory landscape of divergence between stickleback ecotypes and supports a fundamental role for cis-regulatory changes in rapid adaptation to new environments.Competing Interest StatementThe authors have declared no competing interest.