Genome-wide definition of selective sweeps reveals molecular evidence of trait-driven domestication among elite goat (Capra species) breeds for the production of dairy, cashmere, and meat

Abstract

Background: The domestication of wild goats and subsequent intensive trait-driven crossing, inbreeding, and selection have led to dramatic phenotypic purification and intermediate breeds for the high-quality production of dairy, cashmere wool, and meat. Genomic resequencing provides a powerful means for the direct identification of trait-associated sequence variations that underlie molecular mechanisms of domestication.

Results: Here, we report our effort to define such variations based on data from domestic goat breeds (Capra aegagrus hircus; five each) selected for dairy, cashmere, and meat production in reference to their wild ancestors, the Sindh ibex (Capra aegagrus blythi; two) and the Markhor (Capra falconeri; two). Using ∼24 million high-quality single nucleotide polymorphisms (SNPs), ∼1.9 million insertions/deletions, and 2,317 copy number variations, we define SNP-desert-associated genes (SAGs), domestic-associated genes (DAGs), and trait-associated genes (TAGs) and attempt to associate them with quantitative trait loci (QTL), domestication, and agronomic traits. A greater majority of SAGs shared by all domestic breeds are classified into Gene Ontology categories of metabolism and cell cycle. DAGs, together with some SAGs, are most relevant to behavior, immunity, and trait specificity. Whereas, TAGs such as growth differentiation factor 5 and fibroblast growth factor 5 for bone and hair growth, respectively, appear to be directly involved in growth regulation.

Conclusions: When investigating the divergence of Capra populations, the sequence variations and candidate function-associated genes we have identified provide valuable molecular markers for trait-driven genetic mapping and breeding.

Figure 1:

Phylogeny and population structure of goats. (A) PCA based on all identified autosomal SNPs. (B) Neighbor-joining tree based on autosomal SNPs. SN: Saanen dairy goats, LN: Liaoning cashmere goats, and LZ: Leizhou goats. Markhor and Sindh ibex are wild goat ancestors.

Figure 2:

SNP deserts of three domesticated breeds. (A) SNP rate distribution. Mean and median SNP rates are labeled by peaks of distributions. (B) SNP desert length distribution. (C)RSRC1(arginine and serine rich coiled-coil 1) in a SNP desert region shared by all three breeds. SN: Saanen dairy goats, LN: Liaoning cashmere goats, and LZ: Leizhou goats.

Figure 3:

Candidate regions for DAGs. (A) Distribution of Z-transformed pooled heterozygosity (ZHp) in 15 domestic goats, and Z-transformed fixation index (ZFst) between wild and domestic goats for autosomes 1 to 29. Red vertical lines indicate thresholds. (B) Positive end of ZFst distribution (ZFst >3) and negative end of ZHp distribution (ZHp<-3) used for extracting outliers. Dashed lines indicate cutoff values. DAGs labeled are discussed in the text.

Figure 4:

Candidate selective sweep analysis for each economic breed. Selective sweeps and their associated genes are shown in three breeds: (A) Saanen, (B) Liaoning cashmere, and (C) Leizhou. Windows passed the threshold ZFst >4 and the top 1% XP-EHH scores are extracted as selective sweeps. TAGs labeled in color are discussed in the text.

Figure 5:

Opposite selection for sites in GDF5 of dairy and meat breeds. (A) Nonsynonymous SNP T217C (R73G) located in the first exon of GDF5. Amino acids at this position are highly conserved in other mammals. (B) Frequency diverged in different economically relevant traits. Allele T is dominant in the dairy breeds (Saanen and Guanzhong), whereas C is dominant in the meat breeds (Leizhou and Hainan). SN: Saanen goat, LN: Liaoning cashmere goat, LZ: Leizhou goat, GZ: Guanzhong goat, IM: Inner Mongolian cashmere goat, HN: Hainan goat, MA: Markhor, SI: Sindh ibex. Note: Sequencing data are as follows: LZ: CC CC CC CC CC, LN: TC CC CC TC TC, SN: TT TT TT TT TT, MA: TT TT, SI: TT TT.