title: Global view of the evolution and diversity of metazoan neuropeptide signaling.
abstract: Neuropeptides are signaling molecules that commonly act via G protein-coupled receptors (GPCRs) and are generated in neurons by proneuropeptide (pNP) cleavage. Present in both cnidarians and bilaterians, neuropeptides represent an ancient and widespread mode of neuronal communication. Due to the inherent difficulties of analyzing highly diverse and repetitive pNPs, the relationships among different families are often elusive. Using similarity-based clustering and sensitive similarity searches, I obtained a global view of metazoan pNP diversity and evolution. Clustering revealed a large and diffuse network of sequences connected by significant sequence similarity encompassing one-quarter of all families. pNPs belonging to this cluster were also identified in the early-branching neuronless animal Trichoplax adhaerens. Clustering of neuropeptide GPCRs identified several orthology groups and allowed the reconstruction of the phyletic distribution of receptor families. GPCR phyletic distribution closely paralleled that of pNPs, indicating extensive conservation and long-term coevolution of receptor-ligand pairs. Receptor orthology and intermediate sequences also revealed the homology of pNPs so far considered unrelated, including allatotropin and orexin. These findings, together with the identification of deuterostome achatin and luqin and protostome opioid pNPs, extended the neuropeptide complement of the urbilaterian. Several pNPs were also identified from the hemichordate Saccoglossus kowalevskii and the cephalochordate Branchiostoma floridae, elucidating pNP evolution in deuterostomes. Receptor-ligand conservation also allowed ligand predictions for many uncharacterized GPCRs from nonmodel species. The reconstruction of the neuropeptide-signaling repertoire at deep nodes of the animal phylogeny allowed the formulation of a testable scenario of the evolution of animal neuroendocrine systems.
authors: Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany. gaspar.jekely@tuebingen.mpg.de
authors: Gáspár
authors: G
authors: Jékely
mesh_terms: D000818:Animals; D001483:Base Sequence; D002816:Chordata, Nonvertebrate / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D054909:Placozoa / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled
keywords: Petromyzon; Platynereis; proenkephalin
references: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6469-74
references: 10841553
references: Gen Comp Endocrinol. 2012 Dec 1;179(3):331-44
references: 23026496
references: Curr Biol. 2010 Mar 23;20(6):487-95
references: 20226670
references: Cell. 1995 Dec 29;83(7):1263-71
references: 8548812
references: Neuron. 1992 Sep;9(3):505-13
references: 1524828
references: Cell. 2007 Apr 20;129(2):277-88
references: 17448990
references: Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):E1174-83
references: 22006315
references: Evodevo. 2012 Dec 03;3(1):27
references: 23199348
references: Genome Res. 2007 Mar;17(3):320-7
references: 17284679
references: BMC Biol. 2010 Apr 01;8:28
references: 20359331
references: Bioinformatics. 2004 Dec 12;20(18):3702-4
references: 15284097
references: Science. 2009 Dec 4;326(5958):1403-5
references: 19965758
references: Gen Comp Endocrinol. 1999 Feb;113(2):169-86
references: 10082620
references: Biochem Biophys Res Commun. 1995 Nov 22;216(3):1072-8
references: 7488182
references: Genome Biol. 2008;9(8):R131
references: 18717992
references: Nature. 1995 Dec 14;378(6558):730-3
references: 7501021
references: Peptides. 1998;19(8):1425-33
references: 9809658
references: Mol Neurobiol. 2000 Feb-Apr;21(1-2):35-56
references: 11327149
references: Invert Neurosci. 2009 Dec;9(3-4):111-53
references: 20191373
references: J Exp Biol. 1995;198(Pt 3):793-804
references: 9318566
references: Peptides. 1995;16(2):331-8
references: 7784264
references: Nature. 2003 Jun 12;423(6941):762-9
references: 12802337
references: Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6520-5
references: 20308537
references: Front Endocrinol (Lausanne). 2011 Jul 12;2:16
references: 22649364
references: Gen Comp Endocrinol. 2011 Mar 1;171(1):1-16
references: 21185290
references: J Mol Evol. 2002 Jun;54(6):703-14
references: 12029352
references: Ann N Y Acad Sci. 2010 Jul;1200:1-14
references: 20633129
references: Annu Rev Physiol. 1985;47:425-42
references: 2986537
references: Neuron. 2012 Oct 4;76(1):1-11
references: 23040802
references: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1642-7
references: 19164555
references: J Proteome Res. 2010 Oct 1;9(10):5296-310
references: 20695486
references: Mol Cell. 1998 Apr;1(5):673-83
references: 9660951
references: Biochem Biophys Res Commun. 2009 Feb 13;379(3):760-4
references: 19133232
references: J Proteome Res. 2011 Oct 7;10(10):4478-504
references: 21830762
references: Proc Natl Acad Sci U S A. 1987 Aug;84(15):5483-6
references: 3474664
references: Gen Comp Endocrinol. 2010 May 15;167(1):86-103
references: 20171220
references: Peptides. 2010 Mar;31(3):520-4
references: 19781585
references: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11423-8
references: 12177421
references: Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1339-42
references: 18216257
references: Peptides. 2007 Jan;28(1):76-82
references: 17161507
references: Proc Natl Acad Sci U S A. 2013 May 14;110(20):8224-9
references: 23569279
references: Evodevo. 2012 Oct 01;3(1):23
references: 23020891
references: Comp Biochem Physiol C Comp Pharmacol Toxicol. 1986;85(1):219-24
references: 2877794
references: Gen Comp Endocrinol. 2011 Apr 1;171(2):160-75
references: 21241702
references: Curr Biol. 2009 Apr 28;19(8):706-12
references: 19345102
references: Nature. 1987 Dec 10-16;330(6148):537-43
references: 2825030
references: Peptides. 2011 Jun;32(6):1335-55
references: 21440021
references: Science. 2012 Oct 26;338(6106):540-3
references: 23112335
references: Science. 2012 Oct 26;338(6106):543-5
references: 23112336
references: Annu Rev Neurosci. 1992;15:57-85
references: 1575450
references: Cell. 1998 Feb 20;92(4):573-85
references: 9491897
references: J Neurosci. 1998 May 15;18(10):3630-8
references: 9570794
references: J Biol Chem. 2000 Jun 9;275(23):17886-93
references: 10749852
references: Genome Res. 2001 Jun;11(6):1126-42
references: 11381038
references: J Proteome Res. 2010 Apr 5;9(4):2006-15
references: 20163154
references: Insect Biochem Mol Biol. 2009 Mar;39(3):161-70
references: 19063967
references: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14000-5
references: 11717458
references: Endocrinology. 2008 Jun;149(6):2826-39
references: 18339709
references: Biochem Biophys Res Commun. 2011 Jan 7;404(1):184-9
references: 21110953
references: Genome Res. 2008 Jan;18(1):113-22
references: 18025266
references: Science. 2006 Oct 27;314(5799):647-9
references: 17068263
references: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13371-6
references: 19666575
references: Annu Rev Pharmacol Toxicol. 2008;48:393-423
references: 18184105
references: Cell Mol Life Sci. 2011 Jan;68(2):315-23
references: 20652616
references: Curr Biol. 1998 Jul 2;8(14):R477-8
references: 9663378
references: Gen Comp Endocrinol. 2005 May 15;142(1-2):81-93
references: 15862552
references: Cell. 2007 Jun 29;129(7):1389-400
references: 17604726
references: Peptides. 2006 Dec;27(12):3137-53
references: 17049409
references: J Endocrinol. 2006 Sep;190(3):555-70
references: 17003257
references: J Proteome Res. 2008 Sep;7(9):4119-31
references: 18707150
references: Biochem Biophys Res Commun. 1989 May 15;160(3):1015-20
references: 2597281
references: Insect Biochem Mol Biol. 2008 Dec;38(12):1147-57
references: 19280707
references: Comp Biochem Physiol Part D Genomics Proteomics. 2009 Dec;4(4):268-289
references: 20403752
references: Exp Physiol. 2004 May;89(3):229-35
references: 15123557
references: PLoS Biol. 2006 Mar;4(3):e68
references: 16524341
references: Rouxs Arch Dev Biol. 1996 Feb;205(5-6):232-242
references: 28306026
references: Curr Biol. 2006 Jul 25;16(14):1395-407
references: 16860738
references: EMBO J. 1989 May;8(5):1377-84
references: 2569967