Identification and characterization of human taste receptor genes belonging to the TAS2R family

The sense of taste is a chemosensory system responsible for basic food appraisal. Humans distinguish between five primary tastes: bitter, sweet, sour, salty and umami. The molecular events in the perception of bitter taste are believed to start with the binding of specific water-soluble molecules to G-protein-coupled receptors encoded by the TAS2R/T2R family of taste receptor genes. TAS2R receptors are expressed at the surface of taste receptor cells and are coupled to G proteins and second messenger pathways. We have identified, cloned and characterized 11 new bitter taste receptor genes and four new pseudogenes that belong to the human TAS2R family. Their encoded proteins have between 298 and 333 amino acids and share between 23 and 86% identity with other human TAS2R proteins. Screening of a mono-chromosomal somatic cell hybrid panel to assign the identified bitter taste receptor genes to human chromosomes demonstrated that they are located in chromosomes 7 and 12. Including the 15 sequences identified, the human TAS2R family is composed of 28 full-length genes and 16 pseudogenes. Phylogenetic analyses suggest a classification of the TAS2R genes in five groups that may reflect a specialization in the detection of specific types of bitter chemicals.

[1]  N. Ryba,et al.  Mammalian Sweet Taste Receptors , 2001, Cell.

[2]  S. Firestein,et al.  The olfactory receptor gene superfamily of the mouse , 2002, Nature Neuroscience.

[3]  K. Gannon,et al.  Transduction of bitter and sweet taste by gustducin , 1996, Nature.

[4]  K. Beam,et al.  Apical localization of K+ channels in taste cells provides the basis for sour taste transduction. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J F Battey,et al.  Identification of a novel member of the T1R family of putative taste receptors , 2001, Journal of neurochemistry.

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

[7]  C. Dulac,et al.  A Novel Family of Candidate Pheromone Receptors in Mammals , 2000, Neuron.

[8]  B. Lindemann Receptors and transduction in taste , 2001, Nature.

[9]  S. H. Young,et al.  Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Blancher,et al.  The olfactory receptor gene repertoire in primates and mouse: evidence for reduction of the functional fraction in primates. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Mccormick Sequence the Human Genome , 1986, Bio/Technology.

[12]  S. Roper,et al.  Taste Receptor Cells That Discriminate Between Bitter Stimuli , 2001, Science.

[13]  Cynthia Friedman,et al.  Different evolutionary processes shaped the mouse and human olfactory receptor gene families. , 2002, Human molecular genetics.

[14]  B. Trask,et al.  Characterization of nonfunctional V1R-like pheromone receptor sequences in human. , 2000, Genome research.

[15]  Jayaram Chandrashekar,et al.  An amino-acid taste receptor , 2002, Nature.

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

[17]  I. Rodriguez,et al.  A putative pheromone receptor gene expressed in human olfactory mucosa , 2000, Nature Genetics.

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

[19]  N. Chaudhari,et al.  Molecular and Physiological Evidence for Glutamate (Umami) Taste Transduction via a G Protein‐Coupled Receptor a , 1998, Annals of the New York Academy of Sciences.

[20]  P. Mombaerts,et al.  The human repertoire of odorant receptor genes and pseudogenes. , 2001, Annual review of genomics and human genetics.

[21]  N. Ryba,et al.  T2Rs Function as Bitter Taste Receptors , 2000, Cell.

[22]  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.

[23]  International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genome , 2001, Nature.

[24]  N. Chaudhari,et al.  A metabotropic glutamate receptor variant functions as a taste receptor , 2000, Nature Neuroscience.

[25]  J. Desimone,et al.  Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. , 1984, Science.

[26]  H. Weinstein,et al.  Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac , 2001, Nature Genetics.

[27]  Gary D. Stormo,et al.  Displaying the information contents of structural RNA alignments: the structure logos , 1997, Comput. Appl. Biosci..

[28]  Jayaram Chandrashekar,et al.  A Novel Family of Mammalian Taste Receptors , 2000, Cell.

[29]  T. D. Schneider,et al.  Sequence logos: a new way to display consensus sequences. , 1990, Nucleic acids research.

[30]  S. Liberles,et al.  A candidate taste receptor gene near a sweet taste locus , 2001, Nature Neuroscience.