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Title: The evolution and function of melanocortin and melanin-concentrating hormone receptors
Author: Logan, Darren W.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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This thesis describes the cloning, characterisation, evolution and functional role of potential melanogenic genes in the teleost fish, Fugu rubripes and Danio rerio (zebrafish). An in silico analysis of genome trace sequences was carried out to identify fish orthologues of known mammalian genes. The characterised sequences encode a hormonal regulator of mammalian melanogenesis, pro-opiomelanocortin (POMC), its receptors the melanocortin receptor (MCR) family and their functional antagonists, the melanin-concentrating hormone (MCH) receptor family. These studies revealed that zebrafish has six melanocortin receptors, including two MC5R orthologues, whilst Fugu, lacking MC3R, has only four. It is also demonstrated that Fugu and zebrafish have two and three MCH receptor genes respectively and that both have a single POMC gene that appears to be a marker of pituitary development. The discovery in Fugu MC2R and MC5R of an intron located in a uniquely conserved position in both genes, but missing in all other melanocortin receptors genes thus far described, provided an opportunity to investigate the evolution of gene structure in the family. Furthermore, the unusual level of sequence conservation in the codons surrounding the intron meant the analysis could encompass the entire rhodopsin-like G-protein coupled receptor gene family (GPCR-A), of which melanocortin and MCH receptors are members. This investigation revealed that the conserved intron is found within a phylogenetically diverse range of GPCR-As in six vertebrate and invertebrate species, suggesting it is very ancient and has undergone widespread loss. Furthermore, analyses of total intron content in mammalian GPCR-As reveal a large reduction in intron number compared to invertebrate GPCR-A genes. Together, these two lines of investigation provide compelling evidence for the widespread loss of introns during the evolution of the mammalian GPCR-A family. Thus the melanocortin receptor gene family, which was previously thought to have emerged from an intronless ancestor, appears to have once had introns.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available