The G protein-coupled receptor repertoires of human and mouse

Diverse members of the G protein-coupled receptor (GPCR) superfamily participate in a variety of physiological functions and are major targets of pharmaceutical drugs. Here we report that the repertoire of GPCRs for endogenous ligands consists of 367 receptors in humans and 392 in mice. Included here are 26 human and 83 mouse GPCRs not previously identified. A direct comparison of GPCRs in the two species reveals an unexpected level of orthology. The evolutionary preservation of these molecules argues against functional redundancy among highly related receptors. Phylogenetic analyses cluster 60% of GPCRs according to ligand preference, allowing prediction of ligand types for dozens of orphan receptors. Expression profiling of 100 GPCRs demonstrates that most are expressed in multiple tissues and that individual tissues express multiple GPCRs. Over 90% of GPCRs are expressed in the brain. Strikingly, however, the profiles of most GPCRs are unique, yielding thousands of tissue- and cell-specific receptor combinations for the modulation of physiological processes.

[1]  J. Hohmann,et al.  Distribution and regulation of galanin receptor 1 messenger RNA in the forebrain of wild type and galanin-transgenic mice , 2003, Neuroscience.

[2]  S. Foord.  Receptor classification: post genome. , 2002, Current opinion in pharmacology.

[3]  S. Mitaku,et al.  Identification of G protein‐coupled receptor genes from the human genome sequence , 2002, FEBS letters.

[4]  D. Banville,et al.  Proenkephalin A gene products activate a new family of sensory neuron–specific GPCRs , 2002, Nature Neuroscience.

[5]  Alan Wise,et al.  Target validation of G-protein coupled receptors. , 2002, Drug discovery today.

[6]  K. D. Punta,et al.  Multiple new and isolated families within the mouse superfamily of V1r vomeronasal receptors , 2002, Nature Neuroscience.

[7]  David J. Anderson,et al.  A Diverse Family of GPCRs Expressed in Specific Subsets of Nociceptive Sensory Neurons , 2001, Cell.

[8]  Beth Borowsky,et al.  Trace amines: Identification of a family of mammalian G protein-coupled receptors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  F. Echeverri,et al.  The human olfactory receptor repertoire , 2001, Genome Biology.

[10]  Gustavo Glusman,et al.  The complete human olfactory subgenome. , 2001, Genome research.

[11]  G. Mcallister,et al.  Orphan G-protein-coupled receptors and natural ligand discovery. , 2001, Trends in pharmacological sciences.

[12]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[13]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[14]  Z. Csaba,et al.  Cellular biology of somatostatin receptors , 2001, Neuropeptides.

[15]  B. O'dowd,et al.  Orphan G protein-coupled receptors in the CNS. , 2001, Current opinion in pharmacology.

[16]  S. Firestein,et al.  Neurobiology: The good taste of genomics , 2000, Nature.

[17]  Linda B. Buck,et al.  A family of candidate taste receptors in human and mouse , 2000, Nature.

[18]  M. Saraste,et al.  FEBS Lett , 2000 .

[19]  A. Meneses,et al.  5-HT system and cognition , 1999, Neuroscience & Biobehavioral Reviews.

[20]  P. Mombaerts.  Seven-transmembrane proteins as odorant and chemosensory receptors. , 1999, Science.

[21]  J. Bockaert,et al.  Molecular tinkering of G protein‐coupled receptors: an evolutionary success , 1999, The EMBO journal.

[22]  G. Tusnády,et al.  Principles governing amino acid composition of integral membrane proteins: application to topology prediction. , 1998, Journal of molecular biology.

[23]  B. Kobilka,et al.  G protein-coupled receptors: functional and mechanistic insights through altered gene expression. , 1998, Physiological reviews.

[24]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[25]  Roderic D. M. Page,et al.  TreeView: an application to display phylogenetic trees on personal computers , 1996, Comput. Appl. Biosci..

[26]  K. Parker,et al.  The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus. , 1995, Molecular endocrinology.

[27]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[28]  K. Parker,et al.  A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation , 1994, Cell.

[29]  D. Haussler,et al.  Hidden Markov models in computational biology. Applications to protein modeling. , 1993, Journal of molecular biology.

[30]  Richard Axel,et al.  Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium , 1993, Cell.

[31]  Linda B. Buck,et al.  A zonal organization of odorant receptor gene expression in the olfactory epithelium , 1993, Cell.

[32]  K. Parker,et al.  Steroidogenic factor I, a key regulator of steroidogenic enzyme expression, is the mouse homolog of fushi tarazu-factor I. , 1992, Molecular endocrinology.

[33]  R. Axel,et al.  A novel multigene family may encode odorant receptors: A molecular basis for odor recognition , 1991, Cell.

[34]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[35]  Rajesh N. Kalaria, PhD.  Neuropeptides , 1990, Neurology.

[36]  J. Gall,et al.  Molecular hybridization of radioactive DNA to the DNA of cytological preparations. , 1969, Proceedings of the National Academy of Sciences of the United States of America.