title: Concomitant duplications of opioid peptide and receptor genes before the origin of jawed vertebrates.
abstract: BACKGROUND
  The opioid system is involved in reward and pain mechanisms and consists in mammals of four receptors and several peptides. The peptides are derived from four prepropeptide genes, PENK, PDYN, PNOC and POMC, encoding enkephalins, dynorphins, orphanin/nociceptin and beta-endorphin, respectively. Previously we have described how two rounds of genome doubling (2R) before the origin of jawed vertebrates formed the receptor family.
  
  
  RESULTS
  Opioid peptide gene family members were investigated using a combination of sequence-based phylogeny and chromosomal locations of the peptide genes in various vertebrates. Several adjacent gene families were investigated similarly. The results show that the ancestral peptide gene gave rise to two additional copies in the genome doublings. The fourth member was generated by a local gene duplication, as the genes encoding POMC and PNOC are located on the same chromosome in the chicken genome and all three teleost genomes that we have studied. A translocation has disrupted this synteny in mammals. The PDYN gene seems to have been lost in chicken, but not in zebra finch. Duplicates of some peptide genes have arisen in the teleost fishes. Within the prepropeptide precursors, peptides have been lost or gained in different lineages.
  
  
  CONCLUSIONS
  The ancestral peptide and receptor genes were located on the same chromosome and were thus duplicated concomitantly. However, subsequently genetic linkage has been lost. In conclusion, the system of opioid peptides and receptors was largely formed by the genome doublings that took place early in vertebrate evolution.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Görel
authors.initials: G
authors.lastname: Sundström
authors.forename: Susanne
authors.initials: S
authors.lastname: Dreborg
authors.forename: Dan
authors.initials: D
authors.lastname: Larhammar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002645:Chickens; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D007568:Jaw / Q000033:anatomy & histology*; D008969:Molecular Sequence Data; D018847:Opioid Peptides / Q000737:chemistry / Q000235:genetics*; D010802:Phylogeny; D011956:Receptors, Cell Surface / Q000235:genetics; D016415:Sequence Alignment; D026801:Synteny / Q000235:genetics; D014714:Vertebrates / Q000235:genetics*
chemical_list: D018847:Opioid Peptides; D011956:Receptors, Cell Surface
references.citation: Trends Genet. 2004 Nov;20(11):563-9
references.pmid: 15475116
references.citation: Science. 1994 Oct 7;266(5182):117-9
references.pmid: 7939629
references.citation: Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8671-5
references.pmid: 11607217
references.citation: Nature. 2008 Jun 19;453(7198):1064-71
references.pmid: 18563158
references.citation: Biochim Biophys Acta. 2003 Oct 1;1629(1-3):114-8
references.pmid: 14522087
references.citation: Bioessays. 2005 Sep;27(9):937-45
references.pmid: 16108068
references.citation: Brain Res Mol Brain Res. 2003 May 26;114(1):31-9
references.pmid: 12782390
references.citation: Results Probl Cell Differ. 2008;46:1-25
references.pmid: 18193175
references.citation: Cytokine. 1992 Mar;4(2):83-9
references.pmid: 1385987
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15487-92
references.pmid: 18832151
references.citation: J Biol Chem. 2001 Jun 22;276(25):22114-9
references.pmid: 11290742
references.citation: Peptides. 2009 Dec;30(12):2432-79
references.pmid: 19793543
references.citation: Mass Spectrom Rev. 2002 Jul-Aug;21(4):220-43
references.pmid: 12533798
references.citation: Mol Biol Evol. 2009 Apr;26(4):783-99
references.pmid: 19174480
references.citation: Mol Biol Evol. 1992 May;9(3):483-94
references.pmid: 1584015
references.citation: Gen Comp Endocrinol. 2008 Feb 1;155(3):705-16
references.pmid: 17950734
references.citation: Neuropharmacology. 2009;56 Suppl 1:205-12
references.pmid: 18718480
references.citation: Nature. 2006 Feb 23;439(7079):965-8
references.pmid: 16495997
references.citation: Mol Biol Evol. 2005 Dec;22(12):2417-27
references.pmid: 16093565
references.citation: Mol Phylogenet Evol. 2009 Sep;52(3):677-87
references.pmid: 19410007
references.citation: Peptides. 2009 Jul;30(7):1374-82
references.pmid: 19409435
references.citation: J Biol Chem. 2003 Dec 26;278(52):53098-104
references.pmid: 14525992
references.citation: Mol Biol Evol. 2009 Jan;26(1):47-59
references.pmid: 18842688
references.citation: Trends Immunol. 2003 Jul;24(7):387-94
references.pmid: 12860530
references.citation: Gen Comp Endocrinol. 2009 Mar;161(1):3-12
references.pmid: 19007784
references.citation: Bioinformatics. 2002 Mar;18(3):502-4
references.pmid: 11934758
references.citation: Brain Res. 1996 Oct 21;737(1-2):1-15
references.pmid: 8930344
references.citation: BMC Evol Biol. 2005 Nov 08;5:62
references.pmid: 16277660
references.citation: Peptides. 2000 Jul;21(7):1101-9
references.pmid: 10998544
references.citation: Neuroendocrinology. 2002 Jul;76(1):55-62
references.pmid: 12097817
references.citation: BMC Evol Biol. 2008 Jun 25;8:184
references.pmid: 18578868
references.citation: Pharmacol Rev. 2009 Sep;61(3):283-357
references.pmid: 19805477
references.citation: Trends Biochem Sci. 1998 Oct;23(10):403-5
references.pmid: 9810230
references.citation: Mol Biol Evol. 2002 Sep;19(9):1440-50
references.pmid: 12200472
references.citation: Gen Comp Endocrinol. 2006 Aug;148(1):72-8
references.pmid: 16243327
references.citation: Ann N Y Acad Sci. 2005 Apr;1040:22-37
references.pmid: 15891003
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11099-103
references.pmid: 8248214
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Trends Genet. 2005 Oct;21(10):559-67
references.pmid: 16099069
references.citation: Peptides. 2006 Apr;27(4):797-804
references.pmid: 16274850
references.citation: Gen Comp Endocrinol. 2005 May 15;142(1-2):53-9
references.pmid: 15862548