Deep Genome Resequencing Reveals Artificial and Natural Selection for Visual Deterioration, Plateau Adaptability and High Prolificacy in Chinese Domestic Sheep

Abstract

Sheep were one of the earliest domesticated animals. Both artificial and natural selection during domestication has resulted in remarkable changes in behavioral, physiological, and morphological phenotypes; however, the genetic mechanisms underpinning these changes remain unclear, particularly for indigenous Chinese sheep. In the present study, we performed pooled whole-genome resequencing of 338 sheep from five breeds representative of indigenous Chinese breeds and compared them to the wild ancestors of domestic sheep (Asian mouflon, Ovis orientalis) for detection of genome-wide selective sweeps. Comparative genomic analysis between domestic sheep and Asian mouflon showed that selected regions were enriched for genes involved in bone morphogenesis, growth regulation, and embryonic and neural development in domestic sheep. Moreover, we identified several vision-associated genes with funtional mutations, such as PDE6B (c.G2994C/p.A982P and c.C2284A/p.L762M mutations), PANK2, and FOXC1/GMSD in all five Chinese native breeds. Breed-specific selected regions were determined including genes such as CYP17 for hypoxia adaptability in Tibetan sheep and DNAJB5 for heat tolerance in Duolang sheep. Our findings provide insights into the genetic mechanisms underlying important phenotypic changes that have occurred during sheep domestication and subsequent selection.

Keywords: adaptability; domestication; sheep; vision; whole-genome resequencing.

FIGURE 1

Geographic distribution and population genetics analyses of five indigenous Chinese sheep breeds (Ovis aries) and Asian Mouflon (Ovis orientalis). (A) Geographic distribution of five indigenous Chinese sheep breeds (n = 338 sheep). The map was generated uusing Adobe Illustrator CS6 software (https://www.adobe.com/cn/products/illustrator.html). (B) Venn diagram showing the shared single nucleotide polymorphisms (SNPs) between Ovis aries and Ovis orientalis. (C) Venn diagram showing the shared SNPs between the five indigenous Chinese sheep breeds. (D) Principal component (PC) analysis; PC 1 versus PC 2. (E) Neighbor-joining tree. (F) The length and number of indels in five indigenous Chinese sheep breeds and Ovis orientalis. Black and red dots represent the number of insertions and indels, respectively. Colored and gray pillars represent the length of insertions and indels, respectively.

FIGURE 2

Genome-wide selection analyses identified 98 candidate regions associated with domestication. (A) Distribution of Z-transformed average pooled heterozygosity in domestic sheep [H_{P (Domestic sheep)} and Z(H_P)_{Domestic sheep}] and Asian Mouflon [H_{P (Asian Mouflon)} and Z(H_P)_{Asian Mouflon}] as well as average fixation index [F_{ST(Domestic sheep vs. AsianMouflon)} and Z(F_ST)_{Domestic sheep vs. Asian Mouflon}] values for 150-kb windows (σ, standard deviation; μ, average). (B) Plot of the Z(H_P) and Z(F_ST) values for domestic sheep along the sheep genome. A dotted line indicates the cut-off [Z(H_P) ≤ –3.350 and Z(F_ST) ≥ 3.557] used for extracting outliers.

FIGURE 3

Signatures of the selective sweep of the PDE6B gene region in domestic sheep. (A) Heterozygosity (H_P) and fixation index (F_ST) values across a chromosome 6 region harboring the PDE6B gene. The red and green dots represent the H_P value of Ovis aries and Ovis orientalis, respectively. The gray line represents the F_ST values between Ovis aries and Ovis orientalis. (B) Heterozygosity (H_P) and fixation index (F_ST) values around the PDE6B gene region in Asian Mouflon (Ovis orientalis) and five indigenous Chinese sheep breeds. Unbroken and dotted lines represent F_ST and H_P value, respectively. (C) Structure and variations of the PDE6B gene. The pink box and triangle indicate the GAF (cGMP-activated PDEs, adenylyl cyclase, and Fh1A) and HDc (HD/PDEase) domains, respectively. The allele frequencies of four SNPs within the PDE6B gene across five indigenous Chinese sheep breeds and Asian Mouflon (Ovis orientalis).

FIGURE 4

Specific selection regions in each indigenous Chinese sheep breed. (A) Image of Tibetan sheep. (B) Signatures of the selective sweep of the CYP17 gene region associated with hypoxia adaptability in Tibetan sheep. (C) Image of Duolang sheep. (D) Signatures of the selective sweep of the MSRB3 gene region associated with ear size in Duolang sheep. (E) Image of Mongolian sheep. (F) Signatures of the selective sweep of the HoxA gene cluster region associated with vertebral number variations in Mongolian sheep. (G) Image of Hu sheep. (H) Signatures of the selective sweep of the BMPR-IB gene region associated with litter size in Hu sheep. (I) Image of Altay sheep. (J) Signatures of the selective sweep of the T gene region associated with the short-tailed phenotype in Altay sheep.