TITLE: Cis-regulatory divergence between highland and lowland deer mice populations highlight the essential role of pleiotropic genes for high-altitude adaptation.
ABSTRACT: Variation in gene expression regulation contributes extensively to phenotypic diversity within and between species and plays a major role in complex trait evolution. However, the characterization of the genetic basis of regulatory variation is complicated by the inter-dependencies between the expressions of all genes. A promising approach to circumvent this issue is to measure gene-wise allelic imbalance (also known as allele-specific expression) as it intrinsically emphasizes cis-regulatory effects. Here, we demonstrate the power of the allelic imbalance approach and use it to investigate the cis-regulatory landscape of local adaptation to high altitude in the deer mouse (Peromyscus maniculatus). We find evidence that freely segregating regulatory alleles are ubiquitous in wild populations. Then, we detect strong cis-regulatory differentiation between highland and lowland populations in a small set of genes, which comprises known adaptations as well as new candidates and underlines the role of integrative genes to explain the broad range of organismal changes observed in high altitude populations.
