Givaudan-Roure Lecture - Association for Chemoreception Sciences

367 Slide [ ] Taste Genetics and Physiology
GENETICS OF PTC TASTE SENSITIVITY IN HUMANS
Drayna D. 1, Kim U. 2, Wooding S. 3, Jorde L. 4, Floriano W. 5, Goddard
W.A. 5 1National Institute on Deafness and Other Communication
Disor, National Institutes of Health, Rockville, MD; 2NIDCD, National
Institutes of Health, Rockville, MD; 3Genetics, University of Utah, Salt
Lake City, UT; 4Human Genetics, University of Utah, Salt Lake City,
UT; 5Chemistry, California Institute of Technology, Pasadena, CA
The inability of some individuals to taste phenylthiocarbamide (PTC)
was discovered more than 70 years ago and since that time it has been
the subject of detailed studies in genetics, anthropology, and sensory
physiology. We have identified the major gene underlying this trait as
TAS2R38, a G protein coupled bitter taste receptor located on
chromosome 7q. The taster and non-taster forms of this protein differ at
3 amino acid positions, and we have identified other alleles of this gene
that encode various combinations of these 3 variant amino acids, at
least some of which produce intermediate PTC sensitivity. We have
used population genetic methods to study the paradoxical high
frequency of the non-taster form of this gene. Our analyses indicate that
both the major taster and major non-taster alleles have been maintained
by balancing natural selection. Since bitter taste is thought to protect
individuals from ingestion of toxic substances in our diet, this raises the
question of what selective benefit is provided by the non-taster allele.
We hypothesize that the non-taster form of the protein serves as a
functional receptor for a different toxic bitter substance not yet
identified. We have also employed molecular structure prediction
techniques to determine the 3D structure of the taster and non-taster
forms of this receptor, along with PTC ligand binding sites. Our results
indicate that PTC binds to both forms of the receptor with equal
affinity, and that the non-taster form of the protein does not signal due
to a failure of G protein activation.
Supported by NIDCD/NIH Z01-000046 (to D.D.), by NIH grants
ES12125 (to S.W.), GM59290 (to L.J.), and NSF grant BCS0218370
(to L.J.)
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368 Slide [ ] Taste Genetics and Physiology
GENETIC CONTROL OF LICK RATE IN MICE
Boughter J. 1, St. John S. 2, Williams R.W. 3, Lu L. 1 1Anatomy &
Neurobiology, University of Tennessee, Memphis, TN; 2Psychology,
Reed College, Portland, OR; 3Anatomy and Neurobiology, University of
Tennessee, Memphis, Memphis, TN
Licking is a highly stereotyped behavior that is thought to be
determined in part by a central pattern generator (CPG). Lick rate has
been shown to differ among inbred strains of mice, and may play a role
in apparent differences in gustatory sensitivity. We used a 20 minuteaccess
procedure to quantify lick rate in several strains of waterdeprived
mice. Inbred strains could be classified as fast, intermediate,
or slow lickers based on the median value of the inter-lick interval (ILI)
distribution. With virtually no overlap among individual distributions,
C57BL/6J (B6; n = 36) mice were classified as slow lickers (average
median ILI = 122.8 ms) whereas DBA/2J (D2; n = 27) mice were fast
lickers (average median ILI = 101.1). Mice from an F1 generation (n =
14) possessed an intermediate phenotype (112.8 ms). Fast / slow lick
rate phenotypes were static over an extended time period, and were also
evident in non-deprived tests with sucrose. Further testing of an F2
generation (n = 62) resulted in an estimate of broad-sense heritability =
0.54, with no fewer than 2 polymorphic genes influencing the ILI
phenotype. Initial QTL mapping analysis using a panel of BXD RI
strains indicates that at least two and possibly as many as 4 QTL with
comparatively large effects on the ILI are segregating in this cross.
These data will soon be complemented with a genome scan of a panel
of ~ 150 F2 mice that are now being typed using a panel of ~70
microsatellite markers. Additionally, we show how differences in lick
rate between B6 and D2 strains may exert a non-gustatory influence in
lick ratio measurements of sucrose sensitivity. Supported by
DC004935(JDB).
369 Slide [ ] Taste Genetics and Physiology
INTAKE OF SWEET AND BITTER SOLUTIONS: VARIATION
IN INBRED STRAINS OF GOLDEN HAMSTERS
Frank M.E. 1, Wada Y. 2, Makino J. 2, Mizutani M. 2, Umezawa H. 3,
Katsuie Y. 3, Hettinger T.P. 1, Blizard D.A. 4 1Oral Diagnosis,
Neurosciences, UCONN Health Center, Farmington, CT; 2Institute of
Psychology, University of Tsukuba, Tsukuba, Ibaraki, Japan;
3Laboratory Animal Research Station, Nippon Institute for Biological
Science, Kobuchizawa, Yamanashi, Japan; 4Pennsylvania State
University, University Park, PA
Intake of sweet and bitter solutions by 7 inbred strains of golden
hamsters (Mesocricetus auratus), a principal species for studies of
mammalian gustatory systems, was measured. Two concentrations of
sucrose, maltose, D-Phe and Na saccharin, which are sweet; and
quinine·HCl, L-Phe, caffeine and sucrose octaacetate (SOA), which are
bitter to humans, were tested. Difference scores, solution intake minus
mean baseline water intake in mL (DIF), were evaluated by analysis of
variance (α = .05). Compared to ACN, CN, APA, APG and CBN (5
strains with similar DIF for all tested solutions), the strains ACNT and
GN (an ACNT ancestral strain) preferred sucrose, caffeine and SOA
more strongly; ACNT also preferred saccharin and maltose more
strongly and rejected quinine more strongly. There were no strain
differences in DIF for D-Phe or L-Phe. Narrow sense heritabilities for
the 6 compounds for which strain differences were revealed ranged
from 0.31 to 0.57. Genetic correlations indicated the strain variations in
intake of sucrose, saccharin, SOA and caffeine were coupled,
suggesting an association with several possible interpretations. The
genetic differences that influence taste behaviors in existing strains of
hamsters may help identify relevant genes. [Supported by NIH grant
R01 DC04099 (MEF) and a Japan Society Senior Fellowship (DAB)]