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

Abstract

The melanocortin-1 receptor (MC1R) gene influences coloration 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 coloration 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 coloration and other phenotypes.

Beyond mean allelic effects: A locus at the major color geneMC1Rassociates also with differing levels of phenotypic and genetic (co)variance for coloration in barn owls

“…Such epistatic effects are expected from mutations at the MC1R gene given the central role of the encoded protein, which interacts with different ligands to up-or downregulate melanin synthesis (García-Borrón et al 2005). More importantly, we have recently observed an interaction between MC1R genotypes and the expression of the gene PCSK2 in determining melanin content in barn owl feathers, which is in line with a potential physiological epistatic effect of the rufous allele (San-Jose et al 2017). More importantly, we have recently observed an interaction between MC1R genotypes and the expression of the gene PCSK2 in determining melanin content in barn owl feathers, which is in line with a potential physiological epistatic effect of the rufous allele (San-Jose et al 2017).…”

“…More importantly, we have recently observed an interaction between MC1R genotypes and the expression of the gene PCSK2 in determining melanin content in barn owl feathers, which is in line with a potential physiological epistatic effect of the rufous allele (San-Jose et al 2017). Contrarily, melanin synthesis in MC1R RW individuals (no MC1R RR individuals were available for that study) seems to be insensitive to PCSK2, despite that MC1R RW individuals show the same level of expression of this gene as MC1R WW individuals (San-Jose et al 2017). Such an effect is expected given that PCSK2 encodes a protein convertase involved in the cleavage of ACTH into α-MSH, the peptide that binds to MC1R to activate melanin synthesis (Ducrest et al 2008;Galván and Alonso-Alvarez 2009).…”

“…In previous studies, we observed that a valine-to-isoleucine substitution at the amino acid position 126 of the MC1R explains up to 30 % of the variation in plumage coloration in European barn owls (San-Jose et al 2015;Burri et al 2016), and about 5% of the variation in the number and size of the black spots (San-Jose et al 2015). The effect of the rufous and white alleles on the number and size of the spots varies from one body part to another, suggesting potential interactions with other genes controlling coloration (e.g., San-Jose et al 2017). The effect of the rufous and white alleles on the number and size of the spots varies from one body part to another, suggesting potential interactions with other genes controlling coloration (e.g., San-Jose et al 2017).…”

The differential expression of MC1R regulators in dorsal and ventral quail plumages during embryogenesis: Implications for plumage pattern formation

“…Since PC2 is required for generation of α-MSH, from either POMC or ACTH, this strongly suggests that α-MSH is a more important ligand than ACTH in quail, contrary to a suggestion that ACTH might be more important because of its higher binding affinity to MC1R in chicken [41]. Our results are in contrast with a study that found expression of PCSK1 , PCSK2 and POMC in chicken feather follicles [5] but similar to a study that found no detectable expression of PCSK1 in the growing feathers of barn owls ( Tyto alba ) [42]. However, the interpretation is complicated since the two breeds are apigmented (Silky chicken) and barred (Okayama-Jidori), and there was no comparison made between the patterns of gene expression between these breeds.…”

Age‐ and quality‐dependent DNA methylation correlate with melanin‐based coloration in a wild bird

“…To date, the majority of studies of melanin‐based traits have focused on the genes encoding the melanocortin system and characterized either genetic variation between species (Doucet, Shawkey, Rathburn, Mays, & Montgomerie, 2004; Toews et al., 2016) or how mutations in genes like the MC1R are associated with different melanin‐based phenotypes within species (Peters et al., 2016; San‐Jose et al., 2017). So far, only a single study has examined how DNA methylation may impact melanin coloration.…”