Exploring molecular evolution of social behavior in dogs: A study of histone acetylation at GTF2I and its polymorphisms

Abstract

Social behavior is considered one of the major drivers in the evolutionary divergence of modern wolves and dogs. As such, social behavior and its evolution has been linked to macro structural variants across genomes. A previously established variant, gene General Transcription Factor 2-I (GTF2I), has been implicated in social behavior in dogs and humans due to its polymorphisms in the form of transposable element (TE) insertions. This study examines the presence of acetylated histones present at GTF2I and compares samples with and without the TE insertion using Chromatin Immunoprecipitation Sequencing (ChIP-Seq) to better understand whether GTF2I is differentially activated based on polymorphism. There was no significant difference in levels of acetylated histones at GTF2I between samples with and without the TE insertion, however, there was higher histone acetylation within a chromatin region that overlaps GTF2I with the TE insertion and significant enrichment across genes within the Wnt signaling pathway. This is notable due to the Wnt pathway’s role in social behavior in humans with Autism-Spectrum Disorders (ASDs), indicating that findings of enrichment in dog samples may also be related to social behavior. The findings of this study suggest that there is indirect activation of GTF2I in its ancestral polymorphic state containing the TE insertion, contributing to the observed less-social phenotype, and that genome-wide enrichment may contribute to the differences in social behavior between dogs and wolves.