Data from: MC1R variants affect the expression of melanocortin and melanogenic genes and the association between melanocortin genes and coloration

The melanocortin-1-receptor (MC1R) gene influences colouration by altering the expression of genes acting downstream in the melanin synthesis. MC1R belongs to the melanocortin system, a genetic network coding for the ligands that regulate MC1R and other melanocortin receptors controlling different physiological and behavioural traits. The impact of MC1R variants on these regulatory melanocortin genes was never considered, even though MC1R mutations could alter the influence of these genes on coloration (e.g., by decreasing MC1R response to melanocortin ligands). Using barn owl growing feathers, we investigated the differences between MC1R genotypes in the (co)expression of six melanocortin and nine melanogenic-related genes and in the association between melanocortin gene expression and phenotype (feather pheomelanin content). Compared to the MC1R rufous allele, responsible for reddish coloration, the white allele was not only associated with an expected lower expression of melanogenic-related genes (TYR, TYRP1, OCA2, SLC45A2, KIT, DCT) but also with a lower MC1R expression and a higher expression of ASIP, the MC1R antagonist. More importantly, the expression of PCSK2, responsible for the maturation of the MC1R agonist, α-melanocyte-stimulating hormone, was positively related to pheomelanin content in MC1R white homozygotes but not in individuals carrying the MC1R rufous allele. These findings indicate that MC1R mutations not only alter the expression of melanogenic-related genes but also the association between colouration and the expression of melanocortin genes upstream of MC1R. This suggests that MC1R mutations can modulate the regulation of coloration by the pleiotropic melanocortin genes, potentially decoupling the often-observed associations between colouration and other phenotypes.

黑皮质素1受体（melanocortin-1-receptor, MC1R）通过改变黑色素合成通路下游基因的表达，调控动物体色表型。MC1R隶属于黑皮质素系统——一类编码配体的遗传网络，该网络中的配体可调控MC1R及其他黑皮质素受体，进而控制多种生理与行为性状。过往研究从未关注过MC1R变异体对这类调控性黑皮质素基因的影响，尽管MC1R突变可通过降低MC1R对黑皮质素配体的响应等途径，改变这些基因对体色的调控作用。本研究以仓鸮的生长羽毛为实验材料，分析了不同MC1R基因型个体间6个黑皮质素基因与9个黑素生成相关基因的（共）表达差异，以及黑皮质素基因表达与表型（羽毛褐黑素含量）之间的关联。与介导红棕色体色的MC1R红棕色等位基因相比，MC1R白色等位基因不仅与黑素生成相关基因（TYR、TYRP1、OCA2、SLC45A2、KIT、DCT）的预期低表达显著相关，还伴随MC1R自身表达量的降低以及MC1R拮抗剂刺鼠信号蛋白（agouti signaling protein, ASIP）表达水平的升高。更为关键的是，在携带MC1R白色等位基因的纯合个体中，负责激活MC1R的配体——α-黑素细胞刺激素（α-melanocyte-stimulating hormone）的成熟相关基因前蛋白转化酶枯草溶菌素2（PCSK2）的表达量，与褐黑素含量呈正相关；而在携带MC1R红棕色等位基因的个体中未观测到该关联。本研究结果表明，MC1R突变不仅会改变黑素生成相关基因的表达水平，还会改变体色与MC1R上游黑皮质素基因表达之间的关联模式。这提示MC1R突变可调控多效性黑皮质素基因对体色的调控过程，有望打破此前观测到的体色与其他表型之间常见的关联耦合关系。