Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) gene codes a peptide hormone that is important for regulation of emotions such as anxiety and fear. However, genetic influence on the functions remains poorly understood. Here we describe genetic variation and expression diversity of the PACAP gene to identify functional differences that influence and contribute to phenotypic diversity among individual mice (Mus musculus). We have investigated sequence variation of the PACAP gene using genome-wide single-nucleotide polymorphism (SNP) genotypes between wild-caught mice (Mus musculus domesticus, WILD) and laboratory mouse strains (LAB). SNP variations within the groups revealed a significant selective sweep around the PACAP gene in WILD, but not in LAB mice. Gene sequence comparison between the groups showed different length of a dinucleotide (GT) repeat in a intron of the PACAP gene. We found a functional role of this cis-regulatory element so that the GT repeat length affects the expressional pattern of alternative splicing variants of the PACAP gene. These results indicate a contribution of the genetic variation of the PACAP gene to the expression diversity. We speculated that the genetic diversity is associated with functional diversity of PACAP gene that had a role in the establishment of laboratory mouse strains.