Environmentally robustcis-regulatory changes underlie rapid climatic adaptation

Abstract

Changes in gene expression have been proposed to play a major role in adaptive evolution. While it is known that gene expression is highly sensitive to the environment, very few studies have determined the influence of genetic and environmental effects on adaptive gene regulation in natural populations. Here, we utilize allele-specific expression to characterizecisandtransgene regulatory divergence in temperate and tropical house mice in two metabolic tissues under two thermal conditions. First, we show that gene expression divergence is pervasive between populations and across thermal conditions, with roughly 5-10% of genes exhibiting genotype-by-environment interations. Second, we found that most expression divergence was due tocis-regulatory changes that were stable across temperatures. In contrast, patterns of expression plasticity were largely attributable totrans-effects, which showed greater sensitivity to temperature. Nonetheless, we discovered a small subset of temperature-dependentcis-regulatory changes, thereby identifying loci underlying expression plasticity. Finally, we performed scans for selection in wild house mice to identify genomic signatures of rapid adaptation. Genomic outliers were enriched in genes with evidence forcis-regulatory divergence. Notably, these genes were associated with phenotypes that affected body weight and metabolism, suggesting thatcis-regulatory changes are a possible mechanism for adaptive body size evolution between populations. Together, these results highlight how gene regulation changes in response to the environment, and how this regulatory architecture is an important component of adaptation to novel environments.Significance StatementGene expression variation is shaped by both genetic and environmental effects, yet these two factors are rarely considered together in the context of adaptive evolution. We studied environmental influences on gene regulatory evolution in temperate and tropical house mice in cold and warm laboratory environments. We discovered that genetic effects in the form ofcis-regulatory divergence were pervasive and largely insensitive to the environment. Many of these genetic effects are under selection and are associated with genes that affect body size, suggestingcis-regulatory changes as a possible mechanism for adaptive body size evolution. We also discovered manytrans-effects controlling expression plasticity, demonstrating the importance of both genetic and non-genetic changes associated with adaptation over extremeley short timescales (a few hundred generations).