The origin of domestication genes in goats

Abstract

Goat domestication was critical for agriculture and civilization, but its underlying genetic changes and selection regimes remain unclear. Here, we analyze the genomes of worldwide domestic goats, wild caprid species, and historical remains, providing evidence of an ancient introgression event from a West Caucasian tur-like species to the ancestor of domestic goats. One introgressed locus with a strong signature of selection harbors the MUC6 gene, which encodes a gastrointestinally secreted mucin. Experiments revealed that the nearly fixed introgressed haplotype confers enhanced immune resistance to gastrointestinal pathogens. Another locus with a strong signal of selection may be related to behavior. The selected alleles at these two loci emerged in domestic goats at least 7200 and 8100 years ago, respectively, and increased to high frequencies concurrent with the expansion of the ubiquitous modern mitochondrial haplogroup A. Tracking these archaeologically cryptic evolutionary transformations provides new insights into the mechanisms of animal domestication.

Fig. 1. Geographic distribution and genetic affinities of wild and domestic goats used in this study.

(A) Locations of wild (squares), domestic (circles), and ancient (pentagon) goats for each major geographic group. Domestic goats are colored to mirror their geographic origin. BP, before the present. (B) A neighbor-joining tree from the genome sequences used in this study. The branches are colored following the same color code used in (A). (C and D) PCA of bezoars and domestic goats (C) and domestic goats only (D). (E) ADMIXTURE results for k = 3 and k = 6, which had the low cross-validation error.

Fig. 2. Gene flow during the early stage of goat domestication and diffusion.

(A) Geographic distribution of the wild Capra species and the dispersal routes of domestic goats out of their domestication areas (3, 7). Sampling locations for ibex-like species are shown by squares. (B) Allele sharing between modern bezoars (H3) and domestic goats. (C) Allele sharing between domestic goats (H3) and ibex-like species (H1). See also table S8 for other populations (H3) investigated. Statistically significant results, defined by |Z scores| ≥ 3, are marked with a red asterisk for (B) and (C). (D) A scatter plot of introgressed haplotype frequency in EUR-AFR and Asian goat populations. The red dots represent immune-related loci. (E) A heat map of D statistic testing for the differential affinity between SWA (blue) and H2 (red), where H2 represents the individual or population of bezoars and domestic goats located in the map. The East Asian goats are depicted in the box in the upper right corner. (F) Haplotype network from the number of pairwise differences at the MUC6 nonrepeat region. All domestic goats are colored in green, and wild Capra species are divided into five subgroups, including the haplotypes from hybrids of Nubian ibex × domestic goat. The radius of the pie chart and the width of edges were log₂-transformed.

Fig. 3. Genomic regions with selection signals in domestic goats.

(A) Distribution of the pairwise fixation index (F_ST) (x axis), π ln ratio (y axis) and value of XP-EHH (color) between bezoars and domestic goats. The dashed vertical and horizontal lines indicate the significance threshold (corresponding to Z test, P < 0.005, where F_ST > 0.195, π ln ratio > 0.395, and XP-EHH > 2.1) used for extracting outliers. (B) KEGG pathways identified as significantly overrepresented (hypergeometric test, adjusted P < 0.01). (C and D) Selective sweep and distribution of the recombination (RHO) on chromosome 29 (46.22 to 46.31 Mb) (C) and selective sweep on chromosome 15 (32.24 to 32.37 Mb) (D). The putative sweep region is additionally validated by F_ST, Tajima’s D, and CLR test. Horizontal dashed lines represent the whole-genome mean for the corresponding parameters. Gene annotations in the sweep region and SNPs nearly fixed for derived alleles in domestic goats (C and D) are indicated at the bottom.

Fig. 4. The association of MUC6 with gastrointestinal nematodes resistance.

(A) Immunohistochemistry for MUC6 in abomasum pyloric and duodenal bulb of a goat. Photomicrographs at 4× and 20× are shown on the left and in the middle. The negative controls (20×) are shown on the right. (B) The statistical association between MUC6 genotype and the FECs for gastrointestinal nematodes. Wilcoxon rank sum test was used to compute the P values. (C) Manhattan plot of genome-wide association results for FECs. The significant SNPs within MUC6 locus are highlighted in dark green. The dotted horizontal line indicates the threshold (−Log₁₀(P) = 7.65).

Fig. 5. The emergence and diffusion of domestic STIM1-RRM1 and MUC6 haplotypes are concurrent with the spread of mtDNA haplogroup A.

(A) The temporal changes in the frequency of the STIM1-RRM1^D, MUC6^D, and mtDNA haplogroup A from predomestication bezoars to modern domestic goats. The dates are expressed as cal. BP. (B) Genotypes of STIM1-RRM1 and MUC6, and mtDNA and Y-chromosome haplogroups. The presences in homozygous or heterozygous states are shown in green and light green, respectively. The absence of the domestic allele is depicted in light pink. The light gray color symbolizes missing information.