Diversity in chemosensory receptor genes in dogs and wolves: degeneration of the olfactory receptor gene repertoire in the brachycephalic Pug

Dogs, domesticated from gray wolves over 15,000 yr ago, exhibit extensive variation among breeds, including differences in olfactory ability. To investigate the genetic basis of these differences, we analyzed single-nucleotide variants (SNVs) in 3 chemosensory receptor gene families-olfactory receptors (ORs), vomeronasal receptors type 1 (V1Rs), and bitter taste receptors (T2Rs)-using whole-genome data from the Dog Biomedical Variant Database Consortium, which includes 635 domestic dogs representing 121 breeds and 8 wolves. We identified 179 segregating pseudogenes in OR genes (minor allele frequency > 1%), including cases where intact genes are pseudogenized in some individuals and vice versa. The number of functional OR genes varied substantially among individuals (779 to 807), while V1R and T2R gene counts were nearly invariant (8 and 16, respectively). Compared to wolves, dogs exhibited significantly higher ratios of nonsynonymous to synonymous SNVs (N/S) in OR and T2R genes, suggesting relaxed functional constraints potentially associated with domestication. Among breeds, Pugs had significantly fewer functional OR genes and a higher N/S ratio than other breeds, even after accounting for copy number variation. Notably, an OR gene orthologous to the human androstenone receptor, OR7D4, was completely pseudogenized in all Pugs but remained largely functional in other breeds. These findings support the hypothesis that reduced olfactory ability in brachycephalic breeds, such as Pugs, is associated with genetic degeneration of OR genes. Overall, our study provides new insights into the genetic diversity of chemosensory receptor repertoires in dogs and underscores the impact of domestication and breed-specific morphological traits on olfactory function.