Evolution of melanocortin receptors in teleost fish: the melanocortin type 1 receptor

The melanocortin type 1 receptor (Mc1r) belongs to a family of G-protein-coupled receptors involved in various physiological processes in vertebrates. Melanocortins, the Mcr natural agonists, are pituitary peptide hormones including adrenocorticotropin and melanocyte-stimulating hormones. In mammals and birds, Mc1r is involved in pigmentation and expressed in melanocytes and melanoma. Activation of Mc1r leads to eumelanin production as well as to proliferation and survival of melanocytes in the epidermis. Here we report the molecular and evolutionary analysis of mc1r from three major fish models, the zebrafish Danio rerio, the medaka Oryzias latipes and the platyfish Xiphophorus maculatus. In contrast to some other melanocortin receptor genes, mc1r has been conserved as a single copy gene in divergent fish species. Its expression was detected in all organs tested in platyfish and medaka but was restricted to eyes, skin, brain and testis in zebrafish, this possibly reflecting differences in the distribution of extracutaneous melanophores. The mc1r gene was found to be expressed during embryogenesis, as well as in Xiphophorus hybrid melanoma, similar to human tumours. Protein sequence comparison between fish and mammalian Mc1r revealed a remarkable concordance between evolutionary and functional analyses for the identification of residues and regions critical for receptor function.