Molecular evolution of the opioid/orphanin gene family

Gene duplication is a recurring theme in the evolution of vertebrate polypeptide hormones and neuropeptides. These duplication events can lead to the formation of gene families in which divergence of function is the usual outcome. In the case of the opioid/orphanin family of genes, duplication events have proceeded along two paths: (a) an apparent duplication of function as seen in the analgesic activity of Proenkephalin and Prodynorphin end-products; and (b) divergence of function as seen in the nociceptic activity of Proorphanin endproducts or the melanocortin (color change and chronic stress regulation) activity of Proopiomelanocortin endproducts. Although genes coding for Proopiomelanocortin, Proenkephalin, Prodynorphin, and Proorphanin have been extensively studied in mammals, the distribution and radiation of these genes in nonmammalian vertebrates is less well understood. This review will present the hypothesis that the radiation of the opioid/orphanin gene family is the result of the duplication and divergence of the Proenkephalin gene during the radiation of the chordates. To evaluate the Proenkephalin gene duplication hypothesis, a 3'RACE procedure was used to screen for the presence of Prodynorphin-related, Proenkephalin-related, and Proorphanin-related cDNAs expressed in the brains of nonmammalian vertebrates. (C) 1999 Academic Press.