Tracking footprints of artificial selection in the dog genome

Abstract

The size, shape, and behavior of the modern domesticated dog has been sculpted by artificial selection for at least 14,000 years. The genetic substrates of selective breeding, however, remain largely unknown. Here, we describe a genome-wide scan for selection in 275 dogs from 10 phenotypically diverse breeds that were genotyped for over 21,000 autosomal SNPs. We identified 155 genomic regions that possess strong signatures of recent selection and contain candidate genes for phenotypes that vary most conspicuously among breeds, including size, coat color and texture, behavior, skeletal morphology, and physiology. In addition, we demonstrate a significant association between HAS2 and skin wrinkling in the Shar-Pei, and provide evidence that regulatory evolution has played a prominent role in the phenotypic diversification of modern dog breeds. Our results provide a first-generation map of selection in the dog, illustrate how such maps can rapidly inform the genetic basis of canine phenotypic variation, and provide a framework for delineating the mechanistic basis of how artificial selection promotes rapid and pronounced phenotypic evolution.

Fig. 1.

Genomic distribution of population structure in 10 dog breeds. The distribution of d_i for each 1-Mb interval across all autosomes is shown for each breed. Alternating gray and black indicate values in d_i from adjacent chromosomes. The dashed red line denotes the 99th percentile for each breed. Breeds are abbreviated as described in Table 1.

Fig. 2.

Shared versus unique signatures of selection. (A) The number of overlapping signatures of selection in each 1-Mb window is shown. We define an overlapping signature of selection for each window if the empirical P value is ≤ 0.01 in one breed and ≤ 0.05 in another breed. Alternating white and vertical light yellow rectangles indicate adjacent chromosomes. The red arrow indicates the chromosomal region shown in B. (B) (Upper) Sliding-window analyses of pairwise F_ST among German Shepherds, Jack Russell Terriers, and Beagles. Gray boxes indicate two distinct peaks of differentiation (at ≈10.3–10.4 Mb and 11.3–11.4 Mb). Note the different patterns of pairwise F_ST in the two peaks of differentiation. Additional breed comparisons have been omitted for clarity. (Lower) Unrooted neighbor joining trees are shown for all breeds inferred from markers in each of the peaks of differentiation above. Note the distinct topology between the two trees (BGL, JRT, DSH, and BRT lineages are shown in blue).

Fig. 3.

Genetic variation in HAS2 is associated with skin wrinkling in Shar-Pei. (A) Single locus estimates of F_ST between Shar-Pei and Dachshund across a 1-Mb window. Similar patterns were observed for Shar-Pei compared to other breeds, but have been omitted for clarity. The location of all protein-coding genes are shown as rectangular boxes. (B) An example of smooth (Left) and wrinkled (Right) Shar-Pei dogs. (C) Exon structure of HAS2. Conservation values obtained from the University of California Santa Cruz genome browser are shown below. Black horizontal lines indicate sequenced regions. (D) Genotype frequencies of the intron 2 indel (site 13805 in Table S4) in smooth and wrinkled Shar-Pei, which are significantly different (P = 6.28 × 10⁻⁵). Deletion and insertion alleles are denoted as “D” and “d,” respectively.