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Dog Friendliness Associated With Structural Variants in Genes Involved in Human Syndrome

NEW YORK (GenomeWeb) – Researchers have traced the friendliness of dogs to structural variants affecting two genes linked to a human syndrome.

The genes fall in a region that has been linked to Williams-Beuren syndrome, a condition marked by hypersociability, delayed development, and cognitive impairment, among other traits. This suggested to the researchers that hypersociability might have been a key part of the dog domestication process.

An Oregon State University-led team resequenced a 5-megabase stretch of the dog genome that has been under positive selection in domestic dogs and that includes the canine version of the Williams-Beuren locus. They compared alterations in this region to measures of sociability and cognition among dogs and found that structural variants affecting GTF2I and GTFIRD1 contribute to hypersociability among dogs, as they reported today in Science Advances.

"The genetic basis for the behavioral divergence between dogs and wolves has been poorly understood, especially with regard to dogs' success in human environments," senior author Monique Udell from OSU said in a statement. "It was once thought that during domestication, dogs had evolved an advanced form of social cognition that wolves lacked. This new evidence would suggest that dogs instead have a genetic condition that can lead to an exaggerated motivation to seek social contact compared to wolves."

The researchers first examined the sociability of 18 domesticated dogs and 10 captive wolves that had been human-socialized on three measures: attentional bias to social stimuli, hypersociability, and social interest in strangers.

Dogs, they reported, looked to humans more when presented with a puzzle, which reflects greater attentional bias to social stimuli, and they spent more time in proximity to humans than wolves, which indicates increased hypersociability. They noted no statistically significant difference, though, between dogs and wolves in their social interest in strangers.

The researchers then conducted targeted sequencing on a subset of that cohort — 16 dogs and eight wolves — to tie those behaviors to particular genetic alterations. They noted that the canine version of the Williams-Beuren locus that they were targeting appeared to be under positive selection in domesticated dogs.

Through univariate modeling of the three behavioral measures, the researchers linked four structural variants to human-directed social behavior among dogs: a structural variant in GTF2I, one in GTF2IRD1, and two in WBSCR17.

GTF2I and GTF2IRD1 are transcription factors involved in vertebrate development and have been linked to sociability and Williams-Beuren syndrome, the researchers noted. WBSCR17, though, hasn't previously been linked to sociability and instead appears to be involved in carbohydrate metabolism and may reflect an adaptation to a starch-rich diet among dogs, they added.

Through PCR-based analysis, Udell and her colleagues found that the top four loci overlapped with short interspersed nuclear transposable elements. When they examined these insertions in nearly 300 other canids, including coyotes, wolves, and dogs, they found that the transposable elements were largely lacking among coyotes and were present at variable levels among wolves and dogs.

In particular, the researchers found that insertions at two of the loci were associated with increased attentional bias to social stimuli and hypersociability, and insertions at a third locus were linked to increased attentional bias to social stimuli, hypersociability, and social interest in strangers.

Based on their findings, the researchers hypothesized that adult dogs exhibit increased motivation to seek social contact, as compared to adult wolves, and that there's a genetic mechanism guiding their hypersociability that has been acted upon and shaped during domestication.

"This mechanism is expected to predispose dogs for hypersocial responses toward any bonded companion. This is consistent with the finding that domestic dogs appear to maintain, or even increase, the duration of social engagements with humans and [members of the same species] as they approach adulthood, with the opposite trend found in wolves," the researchers wrote in their paper.