Evolution of POMC: origin, phylogeny, posttranslational processing, and the melanocortins

• Published in: Annals of the New York Academy of Sciences Vol. 1220; no. 1; pp. 34 - 48
• Main Authors: Dores, Robert M., Baron, Andrea J.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.03.2011; Wiley Subscription Services, Inc
• Subjects: ACTH; Animals; Chordata; Evolution; Evolution, Molecular; Genomes; Humans; melanocortins; Melanocortins - genetics; Melanocortins - physiology; Narcotics; Origins; Phylogeny; Pituitary gland; POMC; Pro-Opiomelanocortin - genetics; Protein Processing, Post-Translational; α-MSH; β-endorphin
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2010.05928.x

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.