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The proopiomelanocortin (POMC) gene was most likely derived from an ancestral opioid-coding gene following the 1R chordate genome duplication event. During the radiation of the jawless fish, the POMC organization plan emerged multiple melanocortin sequences (α-MSH/ACTH and β-MSH) and a C-terminally extended opioid sequence (β-endorphin). Following the 2R genome duplication event, the γ-MSH sequence was gained. Among the jawed vertebrates, three distinct trends in the evolution of the POMC gene are apparent: the gain of the δ-MSH sequence (cartilaginous fish), the loss of the γ-MSH sequence (ray-finned fish), and the retention of the post 2R POMC organization plan (lobe-finned fish/tetrapods). POMC is synthesized in the pituitary gland and in neurons of the hypothalamus, where an array of posttranslational processing mechanisms, such as endoproteolytic cleavage and N-acetylation, generate distinct sets of end-products in these tissues. A striking feature of the melanocortin end-products is the rigorous conservation of the primary sequence of α-MSH and the first 25 amino acids of ACTH. [ABSTRACT FROM AUTHOR]

In gnathostomes the kappa, mu, delta, ORL-1 receptor genes constitute the opioid/ORL-1 receptor gene family. These genes are most likely the result of two (2R) genome duplication events that occurred during the radiation of the chordates. In stilico analysis of the genome of the lamprey, Petromyzon marius, revealed the partial sequences of four genes that may be the result of a lineage specific genome duplication event in the lamprey lineage. The sequencing of cDNAs from the lamprey CNS supports the assumption that these putative lamprey opioid-like receptor genes are expressed by lamprey neurons. Analysis of gnathostome ORL-1 receptor sequences support the hypothesis that the ORL-1 gene has undergone a transition from an opioid receptor that could bind several types of opioid ligands to a receptor in mammals that can only be activated by the FGGF form of the orphanin ligand. [ABSTRACT FROM AUTHOR]

In 1977 Dr. Robert Schwyzer wrote the review ACTH: A Short Introductory Review, which provided a reference point for current structure/function studies on the interactions between adrenocorticotropic hormone and α-melanocyte-stimulating hormone and the melanocortin receptors. This mini review will evaluate how the predictions made in the 1977 review have held up and also propose a mechanism to explain the ligand selectivity properties of the melanocortin receptors. [ABSTRACT FROM AUTHOR]

The opioid/orphanin gene family provides a model system for analyzing the outcomes of genome duplication events. Recent studies on the proenkephalin gene provide additional evidence that the organizational plan for this gene has been conserved throughout the extensive radiation of the gnathostome vertebrates. However, an analysis of the amino acid sequence of proenkephalin from the zebrafish, Danio rerio, suggests that novel forms of this opioid precursor may be evolving in teleosts. Analyses of sarcopterygian prodynorphin sequences revealed a proenkephalin signature in prodynorphin. Current studies on the opioid/orphanin gene family point to the duplication events that shaped this family occurring prior to the radiation of the gnathostomes. [ABSTRACT FROM AUTHOR]