Skip to main content
SpringerLink
Log in

Novel Neuropeptide Y Y2-Like Receptor Subtype in Zebrafish and Frogs Supports Early Vertebrate Chromosome Duplications

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

The Y receptors comprise a family of G-protein coupled receptors with neuropeptide Y-family peptides as endogenous ligands. The Y receptor family has five members in mammals and evolutionary data suggest that it diversified in the two genome duplications proposed to have occurred early in vertebrate evolution. If this theory holds true, it allows for additional family members to be present. We describe here the cloning, pharmacological characterization, tissue distribution, and chromosomal localization of a novel subtype of the Y-receptor family, named Y7, from the zebrafish. We also present Y7 sequences from rainbow trout and two amphibians. The new receptor is most similar to Y2, with 51–54% identity. As Y2 has also been cloned from some of these species, there clearly are two separate Y2-subfamily genes. Chromosomal mapping in zebrafish supports origin of Y7 as a duplicate of Y2 by chromosome duplication in an early vertebrate. Y7 has probably been lost in the lineage leading to mammals. The pharmacological profile of the zebrafish Y7 receptor is different from mammalian Y2, as it does not bind short fragments of NPY with a high affinity. The Y7 receptor supports the theory of early vertebrate genome duplications and suggests that the Y family of receptors is a result of these early genome duplications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. DA Ammar DM Eadie DJ Wong YY Ma LF, Jr Kolakowski TL Yang-Feng DA Thompson (1996) ArticleTitleCharacterization of the human type 2 neuropeptide Y receptor gene (NPY2R) and localization to the chromosome 4q region containing the type 1 neuropeptide Y receptor gene. Genomics 38 392–398 Occurrence Handle10.1006/geno.1996.0642 Occurrence Handle1:CAS:528:DyaK2sXksFeltQ%3D%3D Occurrence Handle8975716

    Article  CAS  PubMed  Google Scholar 

  2. MM Berglund R Fredriksson E Salaneck D Larhammar (2002) ArticleTitleReciprocal mutations of neuropeptide Y receptor Y2 in human and chicken identify amino acids important for antagonist binding. FEBS Lett 518 5–9 Occurrence Handle10.1016/S0014-5793(02)02534-6 Occurrence Handle1:CAS:528:DC%2BD38XjsVSku7o%3D Occurrence Handle11997008

    Article  CAS  PubMed  Google Scholar 

  3. JM Cerda-Reverter D Larhammar (2000) ArticleTitleNeuropeptide Y family of peptides: structure, anatomical expression, function, and molecular evolution. Biochem Cell Biol 78 371–392 Occurrence Handle10.1139/bcb-78-3-371 Occurrence Handle1:CAS:528:DC%2BD3cXltlKntbw%3D Occurrence Handle10949087

    Article  CAS  PubMed  Google Scholar 

  4. H Doods W Gaida HA Wieland H Dollinger G Schnorrenberg F Esser W Engel W Eberlein K Rudolf (1999) ArticleTitleBIIE0246: A selective and high affinity neuropeptide Y Y(2) receptor antagonist. Eur J Pharmacol 384 R3–R5 Occurrence Handle10.1016/S0014-2999(99)00650-0 Occurrence Handle1:CAS:528:DyaK1MXotVOiu7k%3D Occurrence Handle10611450

    Article  CAS  PubMed  Google Scholar 

  5. Y Dumont JC Martel A Fournier S St-Pierre R Quirion (1992) ArticleTitleNeuropeptide Y and neuropeptide Y receptor subtypes in brain and peripheral tissues. Prog Neurobiol 38 125–167 Occurrence Handle10.1016/0301-0082(92)90038-G Occurrence Handle1:CAS:528:DyaK38XhsVeqsLs%3D Occurrence Handle1312243

    Article  CAS  PubMed  Google Scholar 

  6. DR Gehlert DA Schober SL Gackenheimer L Beavers R Gadski I Lundell D Larhammar (1997) ArticleTitle[125I]Leu31, Pro34-PYY is a high affinity radioligand for rat PP1/Y4 and Y1 receptors: evidence for heterogeneity in pancreatic polypeptide receptors. Peptides 18 397–401 Occurrence Handle10.1016/S0196-9781(96)00346-4 Occurrence Handle1:CAS:528:DyaK2sXivFClt7o%3D Occurrence Handle9145427

    Article  CAS  PubMed  Google Scholar 

  7. M Goumain T Voisin AM Lorinet M Laburthe (1998) ArticleTitleIdentification and distribution of mRNA encoding the Y1, Y2, Y4, and Y5 receptors for peptides of the PP-fold family in the rat intestine and colon. Biochem Biophys Res Commun 241 52–56 Occurrence Handle10.1006/bbrc.1998.8647

    Article  Google Scholar 

  8. P Gregor Y Feng LB DeCarr LJ Cornfield ML McCaleb (1996) ArticleTitleMolecular characterization of a second mouse pancreatic polypeptide receptor and its inactivated human homologue. J Biol Chem 271 27776–27781 Occurrence Handle10.1074/jbc.271.44.27776 Occurrence Handle1:CAS:528:DyaK28XmvVWkt70%3D Occurrence Handle8910373

    Article  CAS  PubMed  Google Scholar 

  9. EL Gustafson KE Smith MM Durkin MW Walker C Gerald R Weinshank TA Branchek (1997) ArticleTitleDistribution of the neuropeptide Y Y2 receptor mRNA in rat central nervous system. Brain Res Mol Brain Res 46 223–235 Occurrence Handle10.1016/S0169-328X(97)00017-X Occurrence Handle1:CAS:528:DyaK2sXislemsL0%3D Occurrence Handle9191097

    Article  CAS  PubMed  Google Scholar 

  10. PW Holland (1999) ArticleTitleGene duplication: past, present and future. Semin Cell Dev Biol 10 541–547 Occurrence Handle10.1006/scdb.1999.0335 Occurrence Handle1:CAS:528:DyaK1MXnvFOmsb0%3D Occurrence Handle10597638

    Article  CAS  PubMed  Google Scholar 

  11. SK Holmberg S Mikko T Boswell R Zoorob D Larhammar (2002) ArticleTitlePharmacological characterization of cloned chicken neuropeptide Y receptors Y1 and Y5. J Neurochem 81 462–471 Occurrence Handle10.1046/j.1471-4159.2002.00817.x Occurrence Handle1:CAS:528:DC%2BD38XjsFGktrk%3D Occurrence Handle12065655

    Article  CAS  PubMed  Google Scholar 

  12. NA Hukriede L Joly M Tsang J Miles P Tellis JA Epstein WB Barbazuk FN Li B Paw JH Postlethwait TJ Hudson LI Zon JD McPherson M Chevrette IB Dawid SL Johnson M Ekker (1999) ArticleTitleRadiation hybrid mapping of the zebrafish genome. Proc Natl Acad Sci USA 96 9745–9750 Occurrence Handle10.1073/pnas.96.17.9745 Occurrence Handle1:CAS:528:DyaK1MXlsVymt7w%3D Occurrence Handle10449765

    Article  CAS  PubMed  Google Scholar 

  13. PD Kelly F Chu IG Woods P Ngo-Hazelett T Cardozo H Huang F Kimm L Liao YL Yan Y Zhou SL Johnson R Abagyan AF Schier JH Postlethwait WS Talbot (2000) ArticleTitleGenetic linkage mapping of zebrafish genes and ESTs. Genome Res 10 558–567

    Google Scholar 

  14. S Kumar K Tamura IB Jakobsen M Nei (2001) ArticleTitleMEGA2: Molecular evolutionary genetics analysis software. Bioinformatics 17 1244–1245 Occurrence Handle1:CAS:528:DC%2BD38XmtVCktQ%3D%3D Occurrence Handle11751241

    CAS  PubMed  Google Scholar 

  15. D Larhammar (1996) ArticleTitleEvolution of neuropeptide Y, peptide YY and pancreatic polypeptide. Regul Pept 62 1–11 Occurrence Handle10.1016/0167-0115(95)00169-7 Occurrence Handle1:CAS:528:DyaK28XjtFWit7g%3D Occurrence Handle8738876

    Article  CAS  PubMed  Google Scholar 

  16. D Larhammar A Wraith MM Berglund SK Holmberg I Lundell (2001) ArticleTitleOrigins of the many NPY-family receptors in mammals. Peptides 22 295–307 Occurrence Handle10.1016/S0196-9781(01)00331-X Occurrence Handle1:CAS:528:DC%2BD3MXisVWntLs%3D Occurrence Handle11287083

    Article  CAS  PubMed  Google Scholar 

  17. I Lundell MM Berglund P Starback E Salaneck DR Gehlert D Larhammar (1997) ArticleTitleCloning and characterization of a novel neuropeptide Y receptor subtype in the zebrafish. DNA Cell Biol 16 1357–1363 Occurrence Handle1:CAS:528:DyaK2sXotFSnu7c%3D Occurrence Handle9407007

    CAS  PubMed  Google Scholar 

  18. LG Lundin (1993) ArticleTitleEvolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse. Genomics 16 1–19 Occurrence Handle10.1006/geno.1993.1133 Occurrence Handle1:CAS:528:DyaK3sXkt1Wnsr4%3D Occurrence Handle8486346

    Article  CAS  PubMed  Google Scholar 

  19. RE Malmstrom T Hokfelt JA Bjorkman C Nihlen M Bystrom AJ Ekstrand JM Lundberg (1998) ArticleTitleCharacterization and molecular cloning of vascular neuropeptide Y receptor subtypes in pig and dog. Regul Pept 75–76 55–70 Occurrence Handle10.1016/S0167-0115(98)00053-6

    Article  Google Scholar 

  20. U Marklund M Bystrom K Gedda A Larefalk K Juneblad S Nystrom AJ Ekstrand (2002) ArticleTitleIntron-mediated expression of the human neuropeptide Y Y(1) receptor. Mol Cell Endocrinol 188 85–97 Occurrence Handle10.1016/S0303-7207(01)00738-9 Occurrence Handle1:CAS:528:DC%2BD38XitFWntro%3D Occurrence Handle11911949

    Article  CAS  PubMed  Google Scholar 

  21. MC Michel A Beck-Sickinger H Cox HN Doods H Herzog D Larhammar R Quirion T Schwartz T Westfall (1998) ArticleTitleXVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev 50 143–150 Occurrence Handle1:CAS:528:DyaK1cXitlylsrc%3D Occurrence Handle9549761

    CAS  PubMed  Google Scholar 

  22. M Nakamura Y Aoki D Hirano (1996) ArticleTitleCloning and functional expression of a cDNA encoding a mouse type 2 neuropeptide Y receptor. Biochim Biophys Acta 1284 134–137 Occurrence Handle10.1016/S0005-2736(96)00166-6 Occurrence Handle1:CAS:528:DyaK28Xlsl2hsr8%3D Occurrence Handle8914576

    Article  CAS  PubMed  Google Scholar 

  23. YK Narnaware RE Peter (2001) ArticleTitleNeuropeptide Y stimulates food consumption through multiple receptors in goldfish. Physiol Behav 74 185–190 Occurrence Handle10.1016/S0031-9384(01)00556-X Occurrence Handle1:CAS:528:DC%2BD3MXmvVyktr4%3D Occurrence Handle11564467

    Article  CAS  PubMed  Google Scholar 

  24. P Naveilhan I Neveu E Arenas P Ernfors (1998) ArticleTitleComplementary and overlapping expression of Y1, Y2 and Y5 receptors in the developing and adult mouse nervous system. Neuroscience 87 289–302 Occurrence Handle10.1016/S0306-4522(98)00141-9 Occurrence Handle1:CAS:528:DyaK1cXlt1eitbc%3D Occurrence Handle9722158

    Article  CAS  PubMed  Google Scholar 

  25. JH Postlethwait YL Yan MA Gates et al. (1998) ArticleTitleVertebrate genome evolution and the zebrafish gene map. Nature Genet 18 345–349 Occurrence Handle1:CAS:528:DyaK1cXit1egsrs%3D Occurrence Handle9537416

    CAS  PubMed  Google Scholar 

  26. PM Rose P Fernandes JS Lynch ST Frazier SM Fisher K Kodukula B Kienzle R Seethala (1995) ArticleTitleCloning and functional expression of a cDNA encoding a human type 2 neuropeptide Y receptor. J Biol Chem 270 29–38 Occurrence Handle10.1074/jbc.270.1.29 Occurrence Handle7814389

    Article  PubMed  Google Scholar 

  27. E Salaneck SK Holmberg MM Berglund T Boswell D Larhammar (2000) ArticleTitleChicken neuropeptide Y receptor Y2: structural and pharmacological differences to mammalian Y2(1). FEBS Lett 484 229–234 Occurrence Handle10.1016/S0014-5793(00)02164-5 Occurrence Handle1:CAS:528:DC%2BD3cXotVCkurs%3D Occurrence Handle11078884

    Article  CAS  PubMed  Google Scholar 

  28. E Salaneck R Fredriksson ET Larson JM Conlon D Larhammar (2001) ArticleTitleA neuropeptide Y receptor Y1-subfamily gene from an agnathan, the European river lamprey. A potential ancestral gene. Eur J Biochem 268 6146–6154 Occurrence Handle10.1046/j.0014-2956.2001.02561.x Occurrence Handle1:CAS:528:DC%2BD3MXptVGqu78%3D Occurrence Handle11733009

    Article  CAS  PubMed  Google Scholar 

  29. P Sharma SK Holmberg H Eriksson AG Beck-Sickinger L Grundemar D Larhammar (1998) ArticleTitleCloning and functional expression of the guinea pig neuropeptide Y Y2 receptor. Regul Pept 75–76 23–28 Occurrence Handle10.1016/S0167-0115(98)00049-4

    Article  Google Scholar 

  30. C Soderberg VA Pieribone J Dahlstrand L Brodin D Larhammar (1994) ArticleTitleNeuropeptide role of both peptide YY and neuropeptide Y in vertebrates suggested by abundant expression of their mRNAs in a cyclostome brain. J Neurosci Res 37 633–640 Occurrence Handle1:STN:280:ByuA3c%2FmsVI%3D Occurrence Handle8028041

    CAS  PubMed  Google Scholar 

  31. P Starback A Wraith H Eriksson D Larhammar (2000) ArticleTitleNeuropeptide Y receptor gene y6: multiple deaths or resurrections? Biochem Biophys Res Commun 277 264–269 Occurrence Handle10.1006/bbrc.2000.3656 Occurrence Handle1:CAS:528:DC%2BD3cXntFOqu70%3D Occurrence Handle11027673

    Article  CAS  PubMed  Google Scholar 

  32. K Strimmer A Haeseler (1996) ArticleTitleQuartet puzzling: A quartet maximum likelihood method for reconstructing tree topologies. Mol Biol Evol 13 964–969 Occurrence Handle1:CAS:528:DyaK28XltlSmsLk%3D

    CAS  Google Scholar 

  33. JS Taylor de Van Y Peer I Braasch A Meyer (2001) ArticleTitleComparative genomics provides evidence for an ancient genome duplication event in fish. Philos Trans R Soc Lond B Biol Sci 356 1661–1679 Occurrence Handle1:CAS:528:DC%2BD38XitFCnsw%3D%3D Occurrence Handle11604130

    CAS  PubMed  Google Scholar 

  34. JD Thompson DG Higgins TJ Gibson (1994) ArticleTitleCLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22 4673–4680 Occurrence Handle7984417

    PubMed  Google Scholar 

  35. A Wagner (1998) ArticleTitleThe fate of duplicated genes: Loss or new function? Bioessays 20 785–788 Occurrence Handle10.1002/(SICI)1521-1878(199810)20:10<785::AID-BIES2>3.0.CO;2-M Occurrence Handle1:STN:280:DyaK1M3gs1emug%3D%3D Occurrence Handle10200118

    Article  CAS  PubMed  Google Scholar 

  36. C Wahlestedt DJ Reis (1993) ArticleTitleNeuropeptide Y-related peptides and their receptors—Are the receptors potential therapeutic drug targets? Annu Rev Pharmacol Toxicol 33 309–352 Occurrence Handle10.1146/annurev.pa.33.040193.001521 Occurrence Handle1:CAS:528:DyaK3sXkvVKisrY%3D Occurrence Handle8494343

    Article  CAS  PubMed  Google Scholar 

  37. IG Woods PD Kelly F Chu P Ngo-Hazelett YL Yan H Huang JH Postlethwait WS Talbot (2000) ArticleTitleA comparative map of the zebrafish genome. Genome Res 10 1903–1914 Occurrence Handle1:CAS:528:DC%2BD3MXht1Y%3D Occurrence Handle11116086

    CAS  PubMed  Google Scholar 

  38. A Wraith A Tornsten P Chardon I Harbitz BP Chowdhary L Andersson LG Lundin D Larhammar (2000) ArticleTitleEvolution of the neuropeptide Y receptor family: Gene and chromosome duplications deduced from the cloning and mapping of the five receptor subtype genes in pig. Genome Res 10 302–310 Occurrence Handle10.1101/gr.10.3.302 Occurrence Handle1:CAS:528:DC%2BD3cXitVWktrg%3D Occurrence Handle10720571

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Christina Bergqvist for excellent technical assistance, Nina Mohell for expert advice on the pharmacological studies, and Björn Carlsson for help with the cAMP assays. Finally, we thank Isabelle Lihrmann and Hubert Vaudry for providing Rana ridibunda genomic DNA and Michael Conlon for providing Xenopus tropicalis genomic DNA. This work was supported by a grant from the Swedish Research Council for Natural and Engineering Sciences (NFR). R.F. was supported by a grant to D.L. from the National Network for the Neurosciences (NNN) of the Swedish Strategic Funds (SSF).

Author information

Authors and Affiliations

  1. Department of Neuroscience, Uppsala University, Box 593, SE-75124, Uppsala, Sweden

    R. Fredriksson, E.T. Larson & D. Larhammar

  2. Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403-1254, USA

    Y.-L. Yan & J.-H. Postlethwait

Authors
  1. R. Fredriksson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E.T. Larson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y.-L. Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J.-H. Postlethwait
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. Larhammar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. Larhammar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fredriksson, R., Larson, E., Yan, YL. et al. Novel Neuropeptide Y Y2-Like Receptor Subtype in Zebrafish and Frogs Supports Early Vertebrate Chromosome Duplications . J Mol Evol 58, 106–114 (2004). https://doi.org/10.1007/s00239-003-2529-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-003-2529-z

Keywords

Search

Navigation