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Observations on the evolution of the melanocortin receptor gene family: distinctive features of the melanocortin-2 receptor.

ABSTRACT: The melanocortin receptors (MCRs) are a gene family in the rhodopsin class of G protein-coupled receptors. Based on the analysis of several metazoan genome databases it appears that the MCRs are only found in chordates. The presence of five genes in the family (i.e., mc1r, mc2r, mc3r, mc4r, mc5r) in representatives of the tetrapods indicates that the gene family is the result of two genome duplication events and one local gene duplication event during the evolution of the chordates. The MCRs are activated by melanocortin ligands (i.e., ACTH, ?-MSH, ?-MSH, ?-MSH, ?-MSH) which are all derived from the polypeptide hormone/neuropeptide precursor, POMC, and as a result the functional evolution of the MCRs is intimately associated with the co-evolution of POMC endocrine and neuronal circuits. This review will consider the origin of the MCRs, and discuss the evolutionary relationship between MC2R, MC5R, and MC4R. In addition, this review will analyze the functional evolution of the mc2r gene in light of the co-evolution of the MRAP (Melanocortin-2 Receptor Accessory Protein) gene family.

SUBMITTER: Dores RM

PROVIDER: S-EPMC3622036 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Observations on the evolution of the melanocortin receptor gene family: distinctive features of the melanocortin-2 receptor.

Dores Robert M RM

Frontiers in neuroscience 20130410

The melanocortin receptors (MCRs) are a gene family in the rhodopsin class of G protein-coupled receptors. Based on the analysis of several metazoan genome databases it appears that the MCRs are only found in chordates. The presence of five genes in the family (i.e., mc1r, mc2r, mc3r, mc4r, mc5r) in representatives of the tetrapods indicates that the gene family is the result of two genome duplication events and one local gene duplication event during the evolution of the chordates. The MCRs are ...[more]

PMID: 23596380

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Project description:Elucidating the mechanisms underlying coevolution of ligands and receptors is an important challenge in molecular evolutionary biology. Peptide hormones and their receptors are excellent models for such efforts, given the relative ease of examining evolutionary changes in genes encoding for both molecules. Most vertebrates possess multiple genes for both the decapeptide gonadotropin releasing hormone (GnRH) and for the GnRH receptor. The evolutionary history of the receptor family, including ancestral copy number and timing of duplications and deletions, has been the subject of controversy.We report here for the first time sequences of three distinct GnRH receptor genes in salamanders (axolotls, Ambystoma mexicanum), which are orthologous to three GnRH receptors from ranid frogs. To understand the origin of these genes within the larger evolutionary context of the gene family, we performed phylogenetic analyses and probabilistic protein homology searches of GnRH receptor genes in vertebrates and their near relatives. Our analyses revealed four points that alter previous views about the evolution of the GnRH receptor gene family. First, the "mammalian" pituitary type GnRH receptor, which is the sole GnRH receptor in humans and previously presumed to be highly derived because it lacks the cytoplasmic C-terminal domain typical of most G-protein coupled receptors, is actually an ancient gene that originated in the common ancestor of jawed vertebrates (Gnathostomata). Second, unlike previous studies, we classify vertebrate GnRH receptors into five subfamilies. Third, the order of subfamily origins is the inverse of previous proposed models. Fourth, the number of GnRH receptor genes has been dynamic in vertebrates and their ancestors, with multiple duplications and losses.Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors. We show that five subfamilies of vertebrate GnRH receptors evolved early in the vertebrate phylogeny, followed by several independent instances of gene loss. Chief among cases of gene loss are humans, best described as degenerate with respect to GnRH receptors because we retain only a single, ancient gene.

Dataset Information

Observations on the evolution of the melanocortin receptor gene family: distinctive features of the melanocortin-2 receptor.

Publications

Observations on the evolution of the melanocortin receptor gene family: distinctive features of the melanocortin-2 receptor.

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