Strong signatures of selection in the domestic pig genome

Abstract

Domestication of wild boar (Sus scrofa) and subsequent selection have resulted in dramatic phenotypic changes in domestic pigs for a number of traits, including behavior, body composition, reproduction, and coat color. Here we have used whole-genome resequencing to reveal some of the loci that underlie phenotypic evolution in European domestic pigs. Selective sweep analyses revealed strong signatures of selection at three loci harboring quantitative trait loci that explain a considerable part of one of the most characteristic morphological changes in the domestic pig--the elongation of the back and an increased number of vertebrae. The three loci were associated with the NR6A1, PLAG1, and LCORL genes. The latter two have repeatedly been associated with loci controlling stature in other domestic animals and in humans. Most European domestic pigs are homozygous for the same haplotype at these three loci. We found an excess of derived nonsynonymous substitutions in domestic pigs, most likely reflecting both positive selection and relaxed purifying selection after domestication. Our analysis of structural variation revealed four duplications at the KIT locus that were exclusively present in white or white-spotted pigs, carrying the Dominant white, Patch, or Belt alleles. This discovery illustrates how structural changes have contributed to rapid phenotypic evolution in domestic animals and how alleles in domestic animals may evolve by the accumulation of multiple causative mutations as a response to strong directional selection.

Fig. 1.

Summary of selective sweep analysis. (A) Striking phenotypic differences between a wild boar and a domestic pig. (B) Genome-wide Z score of heterozygosity (ZHp) plot. The y axis values are −ZHp, and the x axis shows positions of windows along each chromosome. Dotted lines indicate the −ZHp thresholds for inclusion (−4) and bridging/elongation (−3). Red arrows and names indicate loci discussed in the main text. For more comprehensive details on intersections of genes and sweeps, see Table S1 and Fig. S1. (C) Degree of haplotype sharing for the loci overlapping NR6A1, LCORL, and PLAG1 in pairwise comparisons. Boxes to the left indicate the comparison presented on that row (ED, European Domestic; wb, wild boar; AD, Asian Domestic). Heat map colors indicate identity scores. Locations of genes are indicated below the heat map. (D) Body length difference by genotypes at the LCORL and PLAG1 loci. Bar heights show the average length increase relative to homozygotes for the wild-type allele at both loci (WW, wild-type homozygotes; WD, heterozygotes; DD, domestic homozygotes). (E) Results from genotyping wild boars and a diverse panel of European domestic pigs for SNPs in the putative selective sweeps containing NR6A1, PLAG1, and LCORL. The plot is sorted by breeds but has not been clustered by individuals or by breeds. Me, Meishan; AS, Angler Sattelschwein; BS, British Saddleback; HA, Hampshire; mw, Middle White; BB, Bunte Bentheimer; GO, Gloucester Old Spot; LB, Large Black; LS, Linderödssvin; TA, Tamworth; MJ, Manchado de Jabugo; BI, Bisario; NC, Negro Canario; NI, Negro Iberico; RE, Retinto.

Fig. 2.

Excess of derived nonsynonymous substitutions in domestic pigs. Multispecies alignment of four proteins for which domestic pigs are fixed or close to fixation for a derived amino acid substitution, NR6A1 (A), SERPINA6/CBG (B), HK2 (C), and SEMA3D (D). Positions beside protein names indicate the genomic coordinate of missense mutations. Dots indicate identities to the master sequence and dashes indicate missing data.

Fig. 3.

Evolution of white spotting alleles at the KIT locus in pigs. (A) Sequencing depth of coverage for the wild boar- (wild-type), Hampshire- (Belt), and Landrace- (Dominant White) pools demonstrating the presence of three duplications in addition to the previously described DUP1. *Further information on the assembly gap is presented in Fig. S8. Below are magnifications showing sequence conservation in 35 mammals for the DUP2, DUP3, and DUP4 regions. (B) Schematic presentation of our interpretation of porcine KIT alleles. Together, the splice site mutation and the variable copy numbers of the four duplications create great haplotype diversity. **The DUP1 breakpoint (DBP) was precisely defined by Giuffra et al. (49). ***Range of DUP2–4 copy numbers per allele was estimated from quantitative PCR (qPCR) of Belted pigs.