Comparative histomorphometric and transcriptomic analysis reveals potential genetic determinants of pelage variation between hairy and coarse-woolly sheep

Abstract Background The unique pelage composition and developmental pattern endow hairy sheep with superior heat tolerance and minimized wool-shearing needs, compared with coarse-woolly sheep. However, the genetic mechanisms underlying pelage differentiation between these two sheep types remain incompletely understood to date, thereby limiting the development of molecular breeding strategies for cultivating climate-resilient and cost-effective sheep breeds in climate-changing era. Results Through integrated histomorphometric and transcriptomic analysis of Australian White Sheep (AWS, hairy phenotype) and Hu Sheep (HS, coarse-woolly phenotype), we identified three distinct evolutionarily conserved fiber types in AWS (heavily medullated kemp, medullated crimp hair, and non-medullated wool). In contrast, HS exhibited a bimodal fiber distribution without kemp fibers. Compared with AWS, HS had significantly longer hair fibers and markedly reduced subcutaneous adiposity. Transcriptomic profiling identified 370 differentially expressed genes (DEGs): genes enriched in AWS (e.g., DGAT2L6, FOXO6, CIDEA, ADIG) were clustered in lipid metabolism pathways, while genes upregulated in HS (e.g., CSN2, LOC101102413, CSF3R, CXCR2) were significantly associated with immunomodulatory functions. Additionally, hair intermediate filament- and matrix-associated candidate genes (e.g., LOC114113348/KAP20-2, LOC101111178/KRT6A) and EDA2R exhibited breed-specific expression patterns, which were respectively linked to differences in fiber curvature and length. Conclusion Our integrated analysis identifies subcutaneous adiposity and immunoregulation as novel potential key modulators of pelage phenotype divergence between hairy and coarse-woolly sheep—with candidate genes (e.g., KAP20-2, KRT6A, EDA2R) linked to breed-specific fiber traits (e.g., curvature, length). The identified genetic signatures further offer potential actionable targets for precision breeding of climate-resilient and cost-effective sheep, addressing the gap in molecular strategies for pelage-related traits improvement.