4.5 Article

Variants That Differentiate Wolf and Dog Populations Are Enriched in Regulatory Elements

Journal

GENOME BIOLOGY AND EVOLUTION
Volume 13, Issue 4, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/gbe/evab076

Keywords

domestication; cis-regulatory regions; epigenetics

Funding

  1. Swedish Research Council [SNIC 2018011, 2018-05973]
  2. Agria and SKK Forskningsfond

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This study identified highly differentiated variants between wolves and dogs that are enriched in promoters and enhancers. The results highlight the importance of regulatory mutations during dog domestication.
Research on the genetics of domestication most often focuses on the protein-coding exons. However, exons cover only a minor part (1-2%) of the canine genome, whereas functional mutations may be located also in regions beyond the exome, in regulatory regions. Therefore, a large proportion of phenotypical differences between dogs and wolves may remain genetically unexplained. In this study, we identified variants that have high allelic frequency differences (i.e., highly differentiated variants) between wolves and dogs across the canine genome and investigated the potential functionality. We found that the enrichment of highly differentiated variants was substantially higher in promoters than in exons and that such variants were enriched also in enhancers. Several enriched pathways were identified including oxytocin signaling, carbohydrate digestion and absorption, cancer risk, and facial and body features, many of which reflect phenotypes of potential importance during domestication, including phenotypes of the domestication syndrome. The results highlight the importance of regulatory mutations during dog domestication and motivate the functional annotation of the noncoding part of the canine genome.

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