title: Complex structural and regulatory evolution of the pro-opiomelanocortin gene family.
abstract: The melanocortin system is a neuroendocrine machinery that has been associated with phenotypic diversification in a number of vertebrate lineages. Central to the highly pleiotropic melanocortin system is the pro-opiomelanocortin (pomc) gene family, a family of pre-prohormones that each give rise to melanocyte stimulating hormone (MSH), adrenocorticotropic releasing hormone (ACTH), β-lipotropin hormone, and β-endorphin. Here we examine the structure, tissue expression profile, and pattern of cis transcriptional regulation of the three pomc paralogs (α1, α2, and β) in the model cichlid fish Astatotilapia burtoni and other cichlids, teleosts, and mammals. We found that the hormone-encoding regions of pomc α1, pomc α2 and pomc β are highly conserved, with a few notable exceptions. Surprisingly, the pomc β gene of cichlids and pomacentrids (damselfish) encodes a novel melanocortin peptide, ε-MSH, as a result of a tandem duplication of the segment encoding ACTH. All three genes are expressed in the brain and peripheral tissues, but pomc α1 and α2 show a more spatially restricted expression profile than pomc β. In addition, the promoters of each pomc gene have diverged in nucleotide sequence, which may have facilitated the diverse tissue-specific expression profiles of these paralogs across species. Increased understanding of the mechanisms regulating pomc gene expression will be invaluable to the study of pomc in the context of phenotypic evolution.
authors.affiliation: Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, United States; Institute for Cell and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Rayna M
authors.initials: RM
authors.lastname: Harris
authors.affiliation: Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, United States.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Dijkstra
authors.affiliation: Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, United States; Institute for Cell and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States; Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, United States. Electronic address: hans@utexas.edu.
authors.forename: Hans A
authors.initials: HA
authors.lastname: Hofmann
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D029941:Fish Proteins / Q000235:genetics*; D005399:Fishes / Q000235:genetics; D005786:Gene Expression Regulation; D009074:Melanocyte-Stimulating Hormones / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity; D010802:Phylogeny; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D029941:Fish Proteins; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones
keywords: Cichlid; Gene duplication; Genome duplication; Melanocortin system; pomc; ε-MSH