<i>PMEL</i>作为斯布牦牛被毛颜色分化的候选基因：遗传学与功能学解析

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 ( <i>P</i>-adjust<4.47×10 ^- ⁹), with the lead variant (chr5: g.47487664 A>G, <i>P</i>-adjust=2.38×10 ^-10) located within an intron of <i>PMEL</i>. Expression analysis revealed markedly reduced <i>PMEL</i> transcription in fibroblasts from brown individuals. Functional multi-omics analyses of <i>PMEL</i> 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., <i>ADCY7</i>, EDNRA, and epinephrine), PI3K-Akt (e.g., <i>FGF5</i>, <i>PIK3CG</i>, and FGF7), and MAPK (e.g., <i>MAP2K6</i>, <i>FGFR3</i>, and ERBB4) pathways. These findings indicate that the intronic <i>PMEL</i> 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 <i>PMEL</i> as a key candidate gene governing coat color differentiation in Sibu yak.