Assistance dog training programs can see as many as 60% of their trainees dismissed. Many training programs utilize behavioral assays prior to admittance to identify likely successful candidates, yet such assays can be insconsistent. Recently, four canine retrotransposon mobile element insertions (MEIs) in or near genes WBSCR17 (Cfa6.6 and Cfa6.7), GTF2I (Cfa6.66) and POM121 (Cfa6.83) were identified in domestic dogs and gray wolves. Variations in these MEIs were significantly associated with a heightened propensity to initiate prolonged social contact or hypersociability. Using our dataset of 837 dogs, 228 of which had paired survey-based behavioral data, we discovered that one of the insertions in WBSCR17 is the most important predictor of dog sociable behaviors related to human proximity, measured by the Canine Behavioral Assessment Research Questionnaire (C-BARQ©). We found a positive correlation between insertions at Cfa6.6 and dog separation distress in the form of restlessness when about to be left alone by the owner. Lastly, assistance dogs showed significant heterozygosity deficiency at locus Cfa6.6 and higher frequency of insertions at Cfa6.6 and Cfa6.7. We suggest that training programs could utilize this genetic survey to screen for MEIs at WBSCR17 to identify dogs with sociable traits compatible with successful assistance dog performance.

Strong selection on complex traits can lead to skewed trait means and reduced trait variability in populations. An example of this phenomenon can be evidenced in allele frequency changes and skewed trait distributions driven by persistent human-directed selective pressures in domesticated species. Dog domestication is linked to several genomic variants; however, the functional impacts of these variants may not always be straightforward when found in non-coding regions of the genome. Four polymorphic transposable elements (TE) found within non-coding sites along a 5 Mb region on canine CFA6 have evolved due to directional selection associated with heightened human-directed hyper-sociability in domesticated dogs. We found that the polymorphic TE in intron 17 of the canine GTF2I gene, which was previously reported to be negatively correlated with canid human-directed hyper-sociability, is associated with altered chromatin looping and hence distinct cis-regulatory landscapes. We reported supporting evidence of an E2F1-DNA binding peak concordant with the altered loop and higher expression of GTF2I exon 18, indicative of alternative splicing. Globally, we discovered differences in pathways regulating the extra-cellular matrix with respect to TE copy number. Overall, we reported evidence suggesting an intriguing molecular convergence between the emergence of hypersocial behaviors in dogs and the same genes that, when hemizygous, produce human Williams Beuren Syndrome characterized by cranio-facial defects and heightened social behaviors. Our results additionally emphasize the often-overlooked potential role of chromatin architecture in social evolution.

Lowland and highland Peromyscus maniculatus populations display divergent, locally adapted physiological phenotypes shaped by altitudinal differences in oxygen availability. Many physiological responses to hypoxia seem to have evolved in lowland ancestors to offset episodic and localised bouts of low internal oxygen availability. However, upon chronic hypoxia exposure at high elevation, these responses can lead to physiological complications. Therefore, highland ancestry is often associated with evolved hypoxia responses, particularly traits promoting tolerance of constant hypoxia. Environmentally induced DNA methylation can dynamically alter gene expression patterns, providing a proximate basis for phenotypic plasticity. Given each population's differential reliance on plasticity for hypoxia tolerance, we hypothesised that lowland mice have a more robust epigenetic response to hypoxia exposure, driving trait plasticity, than highland mice. Using DNA methylation data of tissues from the heart's left ventricle, we show that upon hypoxia exposure, lowland mice chemically modulate the epigenetic landscape to a greater extent than highland mice, especially at key hypoxia‐relevant genes such as Egln3 . This gene is a regulator of the gene Epas1 that is frequently targeted for positive selection at high elevation. We find higher methylation among wild highland mice at gene Egln3 compared to wild lowland mice, suggesting a shared epigenetic ancestral response to episodic and chronic hypoxia. These findings highlight each population's distinct reliance on molecular plasticity driven by their unique evolutionary histories.