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

Abstract

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.