title: Ancestral vertebrate complexity of the opioid system.
abstract: The evolution of the opioid peptides and nociceptin/orphanin as well as their receptors has been difficult to resolve due to variable evolutionary rates. By combining sequence comparisons with information on the chromosomal locations of the genes, we have deduced the following evolutionary scenario: The vertebrate predecessor had one opioid precursor gene and one receptor gene. The two genome doublings before the vertebrate radiation resulted in three peptide precursor genes whereupon a fourth copy arose by a local gene duplication. These four precursors diverged to become the prepropeptides for endorphin (POMC), enkephalins, dynorphins, and nociceptin, respectively. The ancestral receptor gene was quadrupled in the genome doublings leading to delta, kappa, and mu and the nociceptin/orphanin receptor. This scenario is corroborated by new data presented here for coelacanth and spotted gar, representing two basal branches in the vertebrate tree. A third genome doubling in the ancestor of teleost fishes generated additional gene copies. These results show that the opioid system was quite complex already in the first vertebrates and that it has more components in teleost fishes than in mammals. From an evolutionary point of view, nociceptin and its receptor can be considered full-fledged members of the opioid system.
authors: Department of Neuroscience, Unit of Pharmacology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Electronic address: dan.larhammar@neuro.uu.se.
authors: Dan
authors: D
authors: Larhammar
authors: Department of Neuroscience, Unit of Pharmacology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Christina
authors: C
authors: Bergqvist
authors: Department of Neuroscience, Unit of Pharmacology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Görel
authors: G
authors: Sundström
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018847:Opioid Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D020033:Protein Isoforms / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D008024:Ligands; D009419:Nerve Tissue Proteins; D018847:Opioid Peptides; D020033:Protein Isoforms; D011957:Receptors, Opioid
keywords: Dynorphin; Endorphin; Enkephalin; G protein-coupled receptor; Neuropeptide B; Neuropeptide W; Nociceptin; Opioid; Orphanin FQ; Tetraploidization