@article {Pendleton118794, author = {Amanda L. Pendleton and Feichen Shen and Angela M. Taravella and Sarah Emery and Krishna R. Veeramah and Adam R. Boyko and Jeffrey M. Kidd}, title = {Selective sweep analysis using village dogs highlights the pivotal role of the neural crest in dog domestication}, elocation-id = {118794}, year = {2017}, doi = {10.1101/118794}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Dogs (Canis lupus familiaris) were domesticated from gray wolves between 20-40kya in Eurasia, yet details surrounding the process of domestication remain unclear. The vast array of phenotypes exhibited by dogs mirror numerous 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. We identified 37 candidate domestication regions containing 17.5Mb of genome sequence and 172 genes through whole-genome SNP analysis of 43 globally distributed village dogs and 10 wolves. Comparisons with three ancient dog genomes indicate that these regions reflect signatures of domestication rather than breed formation. Analysis of genes within these regions revealed a significant enrichment of gene functions linked to neural crest cell migration, differentiation and development. Genome copy number analysis identified regions of localized sequence and structural diversity, and discovered additional copy number variation at the amylase-2b locus. Overall, these results indicate that primary selection pressures targeted genes in the neural crest as well as components of the minor spliceosome, rather than genes involved in starch metabolism. Smaller jaw sizes, hairlessness, floppy ears, tameness, and diminished craniofacial development distinguish wolves from domesticated dogs, phenotypes of the Domestication Syndrome that can result from decreased neural crest cells at these sites. We propose that initial selection acted on key genes in the neural crest and minor splicing pathways during early dog domestication, giving rise to the phenotypes of modern dogs.aCGHarray comparative genomic hybridizationCDRcandidate domestication regionchrUnchromosome unknownCNcopy numberCNVcopy number variationddPCRdroplet digital polymerase chain reactionGOgene ontologyNCneural crestNCCneural crest cellqPCRquantitative polymerase chain reactionSNPsingle-nucleotide polymorphismSNRsignal to noise ratioVCDRVST candidate domestication region}, URL = {https://www.biorxiv.org/content/early/2017/03/21/118794}, eprint = {https://www.biorxiv.org/content/early/2017/03/21/118794.full.pdf}, journal = {bioRxiv} }