Comparison of village dog and wolf genomes highlights the pivotal role of the neural crest in dog domestication

Background: Dogs (Canis lupus familiaris) were domesticated from gray wolves between 10-40 kya in Eurasia, yet details surrounding the process of domestication remain unclear. The vast array of phenotypes exhibited by dogs mirror other domesticated animal species, a phenomenon known as the Domestication Syndrome. Here, we use signatures persisting in the dog genome to identify genes and pathways altered by the intensive selective pressures of domestication. Results: We identified 246 candidate domestication regions containing 10.8Mb of genome sequence and 178 genes through whole-genome SNP analysis of 43 globally distributed village dogs and 10 wolves. Comparisons with ancient dog genomes suggest that these regions reflect signatures of domestication rather than breed formation. The strongest hit is located in the Retinoic Acid-Induced 1 (RAI1) gene, mutations of which cause Smith-Magenis syndrome. The identified regions contain a significant enrichment of genes linked to neural crest cell migration, differentiation and development. Read depth analysis suggests that copy number variation played a minor role in dog domestication. Conclusion: Our results indicate that phenotypes distinguishing domesticated dogs from wolves, such as tameness, smaller jaws, floppy ears, and diminished craniofacial development, are determined by genes which act early in embryogenesis. These differences are all phenotypes of the Domestication Syndrome, which can be explained by decreases in neural crest cells at these sites. We propose that initial selection during early dog domestication was for behavior, a trait also influenced by genes which act in the neural crest, which secondarily gave rise to the phenotypes of modern dogs.