Comparative whole-genome resequencing to uncover selection signatures linked to litter size in Hu Sheep and five other breeds.

Hu sheep (HS), a breed of sheep carrying the FecB mutation gene, is known for its "year-round estrus and multiple births" and is an ideal model for studying the high fecundity mechanisms of livestock. Through analyzing and comparing the genomic selection features of Hu sheep and other sheep breeds, we identified a series of candidate genes that may play a role in Hu sheep's high fecundity mechanisms. In this study, we conducted whole-genome resequencing on six breeds and screened key mutations significantly correlated with high reproductive traits in sheep. Notably, the CC2D1B gene was selected by the fixation index (F) and the cross-population composite likelihood ratio (XP-CLR) methods in HS and other five breeds. It was worth noting that the CC2D1B gene in HS was different from that in other sheep breeds, and seven missense mutations have been identified. Furthermore, the linkage disequilibrium (LD) analysis revealed a strong linkage disequilibrium in this specific gene region. Subsequently, by performing different grouping based on FecB genotypes in Hu sheep, genome-wide selective signal analysis screened several genes related to reproduction, such as BMPR1B and PPM1K. Besides, F analysis identified functional genes related to reproductive traits, including RHEB, HSPA2, PPP1CC, HVCN1, and CCDC63. Additionally, a missense mutation was found in the CCDC63 gene and the haplotype was different between the high reproduction (HR) group and low reproduction (LR) group in HS. In summary, we discovered genetic differentiation among six distinct breeding sheep breeds at the whole genome level. Additionally, we identified a set of genes which were associated with reproductive performance in Hu sheep and visualized how these genes differed in different breeds. These findings laid a theoretical foundation for understanding genetic mechanisms behind high prolific traits in sheep.