Evolution of the Neuropeptide Y Receptor Family: Gene and Chromosome Duplications Deduced from the Cloning and Mapping of the Five Receptor Subtype Genes in Pig
- Amanda Wraith1,
- Anna Törnsten2,
- Patrick Chardon3,
- Ingrid Harbitz4,
- Bhanu P. Chowdhary5,
- Leif Andersson2,
- Lars-Gustav Lundin6 and
- Dan Larhammar1,7
- 1Department of Neuroscience, Unit of Pharmacology, Uppsala University, SE-751 24 Uppsala, Sweden; 2Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-751 24 Uppsala, Sweden; 3Laboratoire de Radiobiologie Appliquée, CEA–INRA, Jouy en Josas 78350, France; 4Department of Biochemistry, Physiology and Nutrition, The Norwegian School of Veterinary Science, N-0033 Oslo, Norway; 5Division of Animal Genetics, The Royal Veterinary & Agricultural University, 1870 Frederiksberg, Denmark; 6Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden
Abstract
Neuropeptide Y (NPY) receptors mediate a variety of physiological responses including feeding and vasoconstriction. To investigate the evolutionary events that have generated this receptor family, we have sequenced and determined the chromosomal localizations of all five presently known mammalian NPY receptor subtype genes in the domestic pig, Sus scrofa (SSC). The orthologs of the Y1 and Y2 subtypes display high amino acid sequence identities between pig, human, and mouse (92%–94%), whereas the Y4, Y5, and y6 subtypes display lower identities (76%–87%). The lower identity of Y5 is due to high sequence divergence in the large third intracellular loop. TheNPY1R, NPY2R, and NPY5R receptor genes were localized to SSC8, the NPY4R to SSC14, andNPY6R to SSC2. Our comparisons strongly suggest that the tight cluster of NPY1R, NPY2R, and NPY5R on human chromosome 4 (HSA4) represents the ancestral configuration, whereas the porcine cluster has been split by two inversions on SSC8. These 3 genes, along with adjacent genes from 14 other gene families, form a cluster on HSA4 with extensive similarities to a cluster on HSA5, whereNPY6R and >13 other paralogs reside, as well as another large cluster on HSA10 that includes NPY4R. Thus, these gene families have expanded through large-scale duplications. The sequence comparisons show that the NPY receptor tripletNPY1R–NPY2R–NPY5R existed before these large-scale duplications.
[Sequence data for this article were deposited with the GenBank data library under accession nos.AF106081, PID g6457648 (for Pig Y1 sequence); accession nos. AF106082, PID g4249727 (for Pig Y2 sequence); accession no. AF227955 (for Pig Y4 sequence); accession nos. AF106083, PID g4249729 (for Pig Y5 sequence); accession no. AF227956 (for Pig Y6 sequence).]
Footnotes
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↵7 Corresponding author.
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E-MAIL Dan.Larhammar{at}neuro.uu.se; FAX 46-18 511540.
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- Received September 17, 1999.
- Accepted January 11, 2000.
