MC 1R variants affect the expression of melanocortin and melanogenic genes and the association between melanocortin genes and coloration

Abstract

The melanocortin‐1 receptor ( MC 1R ) gene influences coloration by altering the expression of genes acting downstream in the melanin synthesis. MC 1R belongs to the melanocortin system, a genetic network coding for the ligands that regulate MC 1R and other melanocortin receptors controlling different physiological and behavioural traits. The impact of MC 1R variants on these regulatory melanocortin genes was never considered, even though MC 1R mutations could alter the influence of these genes on coloration (e.g. by decreasing MC 1R response to melanocortin ligands). Using barn owl growing feathers, we investigated the differences between MC 1R 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 MC 1R rufous allele, responsible for reddish coloration, the white allele was not only associated with an expected lower expression of melanogenic‐related genes ( TYR , TYRP 1, OCA 2, SLC 45A2, KIT , DCT ) but also with a lower MC 1R expression and a higher expression of ASIP , the MC 1R antagonist. More importantly, the expression of PCSK 2 , responsible for the maturation of the MC 1R agonist, α‐melanocyte‐stimulating hormone, was positively related to pheomelanin content in MC 1R white homozygotes but not in individuals carrying the MC 1R rufous allele. These findings indicate that MC 1R mutations not only alter the expression of melanogenic‐related genes but also the association between coloration and the expression of melanocortin genes upstream of MC 1R. This suggests that MC 1R mutations can modulate the regulation of coloration by the pleiotropic melanocortin genes, potentially decoupling the often‐observed associations between coloration and other phenotypes.

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