SUPPLEMENTARY TABLES

Transcription

1 Table 1. Human TAS2R genes. Symbol Chromosome, cytogenetic band SUPPLEMENTARY TABLES Genome coordinate, bp Aliases TAS2R1 5p15 9,682,109 T2R1, TRB7 TAS2R2 7p21 12,497,246 T2R2, T2R02 TAS2R16 7q31 122,421,995 T2R16 TAS2R3 7q31 141,110,366 T2R3 TAS2R4 7q31 141,124,758 T2R4 TAS2R5 7q31 141,136,486 T2R5 TAS2R38 7q34 141,318,900 T2R61, PTC, phenylthiocarbamide tasting TAS2R39 7q34 142,590,634 T2R39, T2R57 TAS2R40 7q34 142,629,294 T2R40, T2R58, GPR60 7q34 142,844,250 T2R62, TAS2R62 TAS2R62P TAS2R60 7q35 142,850,668 T2R56; T2R60 TAS2R41 7q35 142,885,088 T2R41, T2R59 TAS2R7 12p13 10,845,398 T2R7, TRB4 TAS2R8 12p13 10,849,917 T2R8, TRB5 TAS2R9 12p13 10,852,960 T2R9, TRB6 TAS2R10 12p13 10,869,212 TRB2, T2R10 TAS2R12 12p13 10,938,800 T2R12, T2R26, TAS2R26 TAS2R13 12p13 10,951,792 TRB3, T2R13 TAS2R14 12p13 10,982,120 TRB1, T2R14 TAS2R15 12p13 11,008,316 T2R15 TAS2R50 12p13 11,029,827 T2R50, T2R51 TAS2R49 12p13 11,040,812 T2R49, T2R56 TAS2R48 12p13 11,065,538 T2R48 TAS2R44 12p13 11,074,274 T2R44, T2R53 TAS2R63P 12p13 11,093,122 T2R63 TAS2R46 12p13 11,105,262 T2R46, T2R54 TAS2R64P 12p13 11,122,108 T2R64, T2R64P TAS2R43 12p13 11,135,168 T2R43, T2R52 TAS2R65P 12p13 11,203,560 T2R65;TAS2R65 TAS2R42 12p13 11,229,866 T2R24, T2R42, T2R55, TAS2R55, T2R55 TAS2R18 TAS2R19 TAS2R20 TAS2R22 TAS2R23 TAS2R30 TAS2R31 TAS2R33 TAS2R36 TAS2R37 TAS2R45 TAS2R47 TAS2R6 T2R18 T2R19 T2R20 T2R22 T2R23 T2R30 T2R31 T2R33 T2R36 T2R37 GPR59, T2R45, ZG24P T2R47 T2R6, T2R06 1

2 Genes are sorted in the order of chromosomal positions. Genes with unassigned genome positions are listed in the end of the table. Pseudogenes have symbols ending with 'P.' Data from the Human Genome Database (GDB), 2

3 Table 2. Mouse Tas2r genes. Symbol Chromosome Chromosome Genome Aliases position, cm coordinate, bp Tas2r134 2 syntenic 51,449,520 T2R134, Tas2r34 Tas2r118 6 syntenic 23,919,163 mgr18, mt2r40, T2R18, Tas2r18 Tas2r137 6 syntenic 40,420,845 mt2r41 Tas2r108 6 syntenic 40,423,199 mgr08, mt2r8, T2R108, T2R8, T2r8 Tas2r138 6 syntenic 40,541,922 mt2r31, T2R138, Tas2r38 Tas2r139 6 syntenic 42,070,543 mt2r34, Tas2r39 Tas2r144 6 syntenic 42,144,935 mt2r33, Tas2r44 Tas2r143 6 syntenic 42,329,845 mt2r36, Tas2r43 Tas2r135 6 syntenic 42,335,136 mt2r38, Tas2r35 Tas2r126 6 syntenic 42,364,142 mgr26, mt2r35, T2R12, T2R26, Tas2r26 Tas2r ,595,585 mt2r42, STC 7-4, T2R30, Tas2r30 Tas2r ,624,851 mgr06, mt2r43, STC 5-1, T2R07, T2R4, Tas2r7 Tas2r ,643,653 mgr06, mt2r44, T2R06, Tas2r6 Tas2r ,650,529 mgr04, mt2r45, T2R04, Tas2r4 Tas2r ,652,254 mgr05, mt2r5, T2R05, T2r5, T2R9, Tas2r5 Tas2r114 6 syntenic 131,654,827 mgr14, mt2r46, T2R14, Tas2r14 Tas2r ,622,650 mgr20, mt2r47, T2R20, Tas2r20 Tas2r ,665,783 mgr21, mt2r48, T2R21, Tas2r21 Tas2r ,702,747 mgr15, mt2r49, T2R15, Tas2r15 Tas2r ,720,423 mgr24, mt2r50, T2R24, Tas2r24 Tas2r ,727,824 mgr02, mt2r51, STC 9-7, Tas2r2 Tas2r ,742,872 mt2r52, Tas2r36 Tas2r145-ps3 6 syntenic 132,752,427 mps3, Tas2r45 Tas2r ,768,594 mgr17, mt2r54, T2R17, Tas2r17 Tas2r111-ps2 6 syntenic 132,786,009 mps2, T2R11 Tas2r ,812,835 mgr23, mt2r55, STC 9-2, T2R23, Tas2r23 Tas2r ,821,131 mgr16, mt2r56, T2R16, Tas2r14, Tas2r16, Tas2r7, TRB1, TRB4 Tas2r ,833,701 mt2r57, STC 9-1, T2R10, Tas2r10 Tas2r ,858,704 mgr13, mt2r58, T2R13, Tas2r13 Tas2r142-ps5 6 syntenic 132,867,627 Tas2r42 Tas2r ,875,344 mgr25, mt2r59, T2R26, 3

4 Tas2r25 Tas2r146-ps1 6 syntenic 132,899,661 mps1, Tas2r46 Tas2r ,916,795 mgr29, mt2r60, T2R29, Tas2r29 Tas2r ,922,605 mgr31, mt2r61, T2R31, Tas2r31 Tas2r ,945,708 mgr09, mt2r62, T2R09, Tas2r9 Tas2r ,020,548 mt2r64, mtrb3, T2R40, Tas2r13, Tas2r40, TRB3, TRB5 Tas2r141-ps4 6 syntenic 133,060,759 Tas2r41 Tas2r mgr03, mt2r63, T2R3, Tas2r10, Tas2r3, TRB2 Tas2r122 6 syntenic mgr22, T2R22, Tas2r22 Tas2r syntenic 32,121,876 mgr19, mt2r19, T2R19, Tas2r19 Genes are sorted in the order of chromosomal positions. Genes with unassigned chromosomal positions in recombination units (cm) are shown as syntenic. Physical (bp) genome positions of Tas2r103 and Tas2r122 are unknown. Pseudogenes have symbols ending with 'ps.' Data from the Mouse Genome formatics (MGI) database, 4

5 Supplementary Table 3. Ligands of the T1R receptors. Ligands vitro vivo T1R1+T1R3 T1R2+T1R3 Tas1r1 KO Tas1r2 KO Tas1r3 KO Tas1r3 KO Tas1r3 alleles Human Human Rat Mouse Rat Mouse Behavior CT Behavior CT Behavior CT Behavior CT GL Behavior CT (8) (8) (10) (8) (12) (4-7) (2) (9) (8) (12) (11) (10) (5-7) (13) (13) (13) (13) (13) (13) (1) (1) (1) (3) (3) Sugars fructose galactose + + a - a glucose + + a - a lactose + + a - a maltose + + a - a palatinose - sucrose -** Sweet proteins brazze in + - monellin neoculin + thaumatin Artificial and natural sweeteners acesulfame K aspartame -** cyclamate dulcin guanidinoacetic acid sweeteners + neohesperidin dihydrochalcone neotame + - saccharin -** SC sorbit ol + steviozide + + sucralose Amino acids D-alanine +* D-asparginine -** D-aspartate -** D-glutamate -** -** D-glutamine -** + 1

6 D-histidine -** + D-phenylalanine -** D-tryptophan -** -** glycine -** L-alanine * + +* - L-arginine + +* +* L-asparginine + - +* +* L-aspartate +* +* +* +* +* L-cysteine + L-glutamate + + +* * + +* + + -** - L-glutamine -** + - L-histidine -** + L-isoleucine +* L-leucine -** +* L-lysine -** +* L-methionine + L-phenylalanine +* - L-proline -** +* - - L-serine -** * + +* L-threonine + - L-tryptophan -** - - L-tyrosine -** L-valine + Umami compounds IM P L-AP4 +* -** +* +* +* Responses only to sweet, umami -tasting stimuli and amino acids are shown. Responses of mouse and human T1R1 + T1R3 in vitro were potentiated by IMP. + vitro: a response to a taste stimulus; in vivo: effect on response to a taste stimulus. - vitro: lack of a response to a taste stimulus; in vivo: lack of effect on response to a taste stimulus. * vitro: a response only when the taste stimulus is applied with IMP, but no response without IMP; in vivo: effect on a response to a taste stimulus mixed with IMP. **No response with or without IMP. a Rat T1R2 + T1R3 responded to galactose, glucose, lactose and maltose in (8) study but not in (11) study. The difference in responses patterns was suggested to be attributed to different G proteins co-transfected with T1Rs: Gα15 and Gα16-Gz (11) or Gα15/i1 (8). 2

7 REFERENCES 1. Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Varadarajan V, et al Detection of sweet and umami taste in the absence of taste receptor T1r3. Science 301: Galindo-Cuspinera V, Winnig M, Bufe B, Meyerhof W, Breslin PA A TAS1R receptor-based explanation of sweet 'water-taste'. Nature 441: oue M, Reed DR, Li X, Tordoff MG, Beauchamp GK, Bachmanov AA Allelic variation of the Tas1r3 taste receptor gene selectively affects behavioral and neural taste responses to sweeteners in the F 2 hybrids between C57BL/6ByJ and 129P3/J mice. J Neurosci 24: Jiang P, Cui M, Ji Q, Snyder L, Liu Z, et al Molecular mechanisms of sweet receptor function. Chem Senses 30 Suppl 1: i17-i8 5. Jiang P, Cui M, Zhao B, Liu Z, Snyder LA, et al Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. J Biol Chem 280: Jiang P, Cui M, Zhao B, Snyder LA, Benard LM, et al Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. J Biol Chem 280: Jiang P, Ji Q, Liu Z, Snyder LA, Benard LM, et al The cysteine-rich region of T1R3 determines responses to intensely sweet proteins. J Biol Chem 279: Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A 99: Nakajima K, Asakura T, Oike H, Morita Y, Shimizu-Ibuka A, et al Neoculin, a taste-modifying protein, is recognized by human sweet taste receptor. Neuroreport 17: Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, et al An amino-acid taste receptor. Nature 416: Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS Mammalian sweet taste receptors. Cell 106: Winnig M, Bufe B, Meyerhof W Valine 738 and lysine 735 in the fifth transmembrane domain of rtas1r3 mediate insensitivity towards lactisole of the rat sweet taste receptor. BMC Neurosci 6: Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, et al The receptors for mammalian sweet and umami taste. Cell 115:

8 Supplementary Table 4. Ligands of the T2R receptors. Species: Rat Mouse Mouse Human Chimpanzee Human Human Human Human Human Human Human Gene symbol: Tas2r105* Tas2r105* Tas2r108** TAS2R4** TAS2R38*** TAS2R38*** TAS2R10 TAS2R14 TAS2R16 TAS2R43 TAS2R44 TAS2R47 mt2r5, ht2r38, ht2r10, ht2r43, ht2r44, mt2r8, ht2r4, ht2r16, T2R05, T2r5, T2R38, T2R10, ht2r14, TR43, TR44, TR47, rt2r9, T2R108, T2R4, T2R16, Synonyms: T2R9, ht2r61, hgr10, T2R14,hGR14, ht2r61, ht2r53, ht2r44, T2R9 T2R8, T2r8 T2R04, hgr16, Tas2r5 T2R61, T2RA, T2RE, TRB1 ht2r52, T2R53, T2R44 mgr08 hgr04 T2RC mgr05 T2R51, PTC TRB2 TR52 TR53, T2R64 Approach: vitro References: (4) vitro (5, 16, 18) vivo (13, 14) vitro vivo vitro vivo vitro a vivo vitro a (5) (6) (5) (6) (19) (19) (3) vivo (3, 7, 10, 12, 13, 15) vitro vitro (4) (1, 2) vitro (1, 4, 9, 17, 18) vivo (6, 13) vitro vitro vitro (1, 11, 16) (8, 11) (16) Cycloheximide Lidocaine + Denatonium Strychnine + Aristolochic acid + + Saccharin + + Acesulfame K nitrosaccharin + + N-isopropyl-2-methyl-5- nitrobenzenesulfonamide + picrotoxinin + picrotin + piperonylic acid + sodium benzoate + 1,8-naphthalaldehydic acid + 1-naphtolic acid + 1-nitronaphthalene + (-)-α -thujone + Thioamides: phenylthiocarbamide (PTC) propylthiouracil (PROP) diphenylthiurea + acetylthiourea + methylthiouracil + Beta-glucopyranosides: salicin + helicin + arbutin + amygdalin + esculin + phenyl-β-dglucopyranoside nitrophenyl-β-Dglucopyranoside + naphtyl-β-dglucopyranoside + methyl-β-dglucopyranoside + 1

9 a Ligands of a PTC-sensitive allele of human and chimpanzee TAS2R38. Asterisks indicate orthologs: *mouse and rat Tas2r105; **human TAS2R4 and mouse Tas2r108; ***human and chimpanzee TAS2R38. vitro studies used heterologous expression in cell cultures. vivo studies used several approaches: positional cloning (10), genotype-phenotype association in humans (3, 7, 12, 15), chimpanzee (20) and mouse (5, 14), knockout mice (13), transgenic expression of human T2R genes in the mouse taste receptor cells (13), and transgenic expression of human and mouse T2R genes in Caenorhabditis elegans (6). 2

10 REFERENCES 1. Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W Members of RTP and REEP gene families influence functional bitter taste receptor expression. J Biol Chem 281: Behrens M, Brockhoff A, Kuhn C, Bufe B, Winnig M, Meyerhof W The human taste receptor htas2r14 responds to a variety of different bitter compounds. Biochem Biophys Res Commun 319: Bufe B, Breslin PA, Kuhn C, Reed DR, Tharp CD, et al The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr Biol 15: Bufe B, Hofmann T, Krautwurst D, Raguse JD, Meyerhof W The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides. Nat Genet 32: Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, et al T2Rs function as bitter taste receptors. Cell 100: Conte C, Guarin E, Marcuz A, Andres-Barquin PJ Functional expression of mammalian bitter taste receptors in Caenorhabditis elegans. Biochimie 88: Duffy VB, Davidson AC, Kidd JR, Kidd KK, Speed WC, et al Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake. Alcohol Clin Exp Res 28: Galindo-Cuspinera V, Winnig M, Bufe B, Meyerhof W, Breslin PA A TAS1R receptor-based explanation of sweet 'water-taste'. Nature 441: Hinrichs AL, Wang JC, Bufe B, Kwon JM, Budde J, et al Functional variant in a bitter-taste receptor (htas2r16) influences risk of alcohol dependence. Am J Hum Genet 78: Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299: Kuhn C, Bufe B, Winnig M, Hofmann T, Frank O, et al Bitter taste receptors for saccharin and acesulfame K. J Neurosci 24: Mennella JA, Pepino MY, Reed DR Genetic and environmental determinants of bitter perception and sweet preferences. Pediatrics 115: e Mueller KL, Hoon MA, Erlenbach I, Chandrashekar J, Zuker CS, Ryba NJ The receptors and coding logic for bitter taste. Nature 434: Nelson TM, Munger SD, Boughter JD, Jr Taste sensitivities to PROP and PTC vary independently in mice. Chem Senses 28: Prodi DA, Drayna D, Forabosco P, Palmas MA, Maestrale GB, et al Bitter taste study in a sardinian genetic isolate supports the association of phenylthiocarbamide sensitivity to the TAS2R38 bitter receptor gene. Chem Senses 29: Pronin AN, Tang H, Connor J, Keung W Identification of ligands for two human bitter T2R receptors. Chem Senses 29: Soranzo N, Bufe B, Sabeti PC, Wilson JF, Weale ME, et al Positive selection on a high-sensitivity allele of the human bitter-taste receptor TAS2R16. Curr Biol 15:

11 18. Ueda T, Ugawa S, Yamamura H, Imaizumi Y, Shimada S Functional interaction between T2R taste receptors and G-protein alpha subunits expressed in taste receptor cells. J Neurosci 23: Wooding S, Bufe B, Grassi C, Howard MT, Stone AC, et al dependent evolution of bitter-taste sensitivity in humans and chimpanzees. Nature 440: Wooding S, Kim UK, Bamshad MJ, Larsen J, Jorde LB, Drayna D Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. Am J Hum Genet 74:

12 Supplementary Figure 1. Chromosomal positions of human TAS1R (chromosome 1) and TAS2R (chromosomes 5, 7 and 12) genes. Data from the Human Genome Database (GDB), 1

13 Supplementary Figure 2. Structure of the mouse Tas1r genes (left) and Tas2r genes (right; exemplified by Tas2r134). Boxes indicate exons. The mouse Tas1r genes contain 6 coding exons and 5 introns. The mouse Tas2r genes are intronless. Data from the Mouse Genome formatics (MGI) database, 2

14 Supplementary Figure 3. Alternative splicing of the human TAS1R1 gene. Boxes indicate exons for four alternatively spliced transcripts (a, b, c and d). Data from the National Center for Biotechnology formation (NCBI) database, 3