PMEL as a candidate gene for coat color differentiation in Sibu yaks: Genetic and functional insights

Coat color represents a key phenotypic trait in Sibu yak, exhibiting distinct black and brown phenotypes. To elucidate the genetic basis of the brown phenotype, genome-wide association studies and multi-omics analyses were integrated to identify loci and molecular pathways involved in pigmentation. In total, 11 single-nucleotide polymorphisms (SNPs) on chromosome (chr) 5 displayed genome-wide significance ( P-adjust<4.47×10 ^{- 9}), with the lead variant (chr5: g.47487664 A>G, P-adjust=2.38×10 ^-10) located within an intron of PMEL. Expression analysis revealed markedly reduced PMEL transcription in fibroblasts from brown individuals. Functional multi-omics analyses of PMEL overexpression demonstrated significant alteration of the expression of 1 088 genes, 444 proteins, and 57 metabolites. Enrichment analyses indicated significant involvement of melanogenesis-related signaling cascades, including cAMP (e.g., ADCY7, EDNRA, and epinephrine), PI3K-Akt (e.g., FGF5, PIK3CG, and FGF7), and MAPK (e.g., MAP2K6, FGFR3, and ERBB4) pathways. These findings indicate that the intronic PMEL variant modulates gene expression and pigmentation through coordinated regulation of these pathways, thereby contributing to the phenotypic divergence of Sibu yak coat color. This study provides valuable insights into the genetic mechanisms underlying Sibu yak pigmentation and identifies PMEL as a key candidate gene governing coat color differentiation in Sibu yak.