Evolution of phenylthiocarbamide taster trait in Mysore, South India.

BACKGROUND: The ability to taste phenylthiocarbamide (PTC), a bitter chemical has long been known to be a heritable trait, which is being widely used for both genetic and anthropological studies. The frequency of taster and non-taster allele is found to vary in different populations. AIMS AND
OBJECTIVE: To investigate the frequency of taster trait in Mysore, South India.
MATERIALS AND METHODS: The present investigation was conducted in Mysore, South India during 2002 - 2003. About 3282 subjects irrespective of age, sex, religion, food habits, socio-economic status were randomly selected from various parts of the city and a total of 180 families, which included Christian (50), Hindu (61) and Muslim (69) were screened from different localities of the city. Harris and Kalmus method was used to assess the PTC taster and nontaster phenotype.
RESULTS: It was found that tasters were significantly more frequent than nontasters in all the four categories. The incidence of tasters was more in unbiased category (85%) and less in Muslim category (58%). Investigations on PTC tasting in the families of three different religious groups revealed that the tasters were significantly more frequent than nontasters. It was also found that heterozygous father or mother for the taster genes with nontaster partner had taster and nontaster progenies in the ratio 1.0: 1.54 indicating the deviation in the segregation pattern of test cross.
CONCLUSION: In Mysore, tasters are more frequent than nontasters. Variation in the frequency of nontaster allele in the religious groups could be due to inbreeding.

Introduction

Phenylthiocarbamide (PTC), a bitter chemical synthesized by Fox[1] has been widely used for genetic and anthropological studies.[2] Taste responsiveness to PTC was known to be a heritable trait. The inability to taste PTC is a simple Mendelian recessive trait,[3-7] wherein the individuals with two recessive alleles (tt) are nontasters for PTC and individuals with one dominant allele (Tt) or two dominant alleles (TT) are tasters for PTC. There are many reports, which contradict this model, some of them are: incomplete dominance,[8] two locus model[9-12] and polygenic model.[13]

Kim et al[2] have identified a small region on Chromosome 7q by genome-wide linkage analysis, which shows strong linkage disequilibrium between single-nucleotide polymorphism markers and PTC taste sensitivity in unrelated subjects. This region harbors a gene that encodes a member of the TAS2R bitter taste receptor family. A major locus on 7q35-q36 and a secondary locus on Chromosome 16p have also been localized by genome scan for PTC taster gene.[12] Bufe et al[14] have demonstrated that alleles of hTAS2R38 codes for functionally different receptor types that directly affect bitterness perception containing compounds. They suggested that these polymorphisms might be due to evolutionary pressures that foster variability at the receptor to enhance bitter detection and rejection of these compounds. In the present study, we report that the tasters are more frequent than nontasters in Mysore, South India.

Materials and Methods

The present investigation was conducted in Mysore, South India from 2002-2003. About 3282 subjects were randomly selected from various parts of the city irrespective of age, sex, religion, food habits and socio-economic status. Subjects were classified into four different categories viz, unbiased category (= individuals screened randomly in public places without looking into religion, region, age and sex), Hindu, Christian and Muslim religious groups. In order to assess the pattern of inheritance and the frequency of the PTC tasting in different religious groups, a total of 180 families, which included Christian (50), Hindu (61) and Muslim (69) were screened from different localities of the city.

Harris and Kalmus[7] method was used to assess the PTC taster and nontaster phenotype. With their consent, the subjects and their family members were asked to taste the PTC solution and the results were recorded in the proforma used to collect the family history. Information about any possible migration in or out of these families or any associated diseases in the family was also recorded. Pedigrees were constructed based on the information collected from these families. Chi square test was applied to justify the deviations from the expected ratio of taster and nontaster alleles.

One of the limitations of this study was, the number of offspring born in these families were less. However, this can be justified by the fact that in humans each conception is an independent event; the probability of having another child in these families who could be a taster cannot be ruled out. Another limitation is that the availability of families over three to four generations is very rare and even some of these families were not given consent for this study.

Results

PTC taster trait was analyzed in four different categories namely Unbiased, Hindu, Muslim and Christian groups. It was found that tasters were significantly more frequent than nontasters in all the four categories [Table 1]. The incidence of tasters was more in the unbiased category (85%) and less in the Muslim category (58%). Based on the taster phenotype of the progeny and the parents analyzed in 180 families, five different genotypic groups were classified. They are (a) TT ♂ × TT ♀, (b) Tt ♂ × Tt ♀, (c) TT(t) ♂ × tt ♀, (d) tt ♂ × TT(t) ♀ and (e) tt ♂ × tt ♀. Pedigrees were constructed for all the five different genotypic groups [Figure 1]. Of the 180 families studied, parents of 55 families were in homozygous dominant for taster trait and parents of 12 families were in heterozygous condition [Table 2]. Taster parents (67 families) had produced both taster and nontaster children, of which 89% were taster children, whereas nontaster parents (27 families), had produced only nontaster children (100%). Figure 2 illustrates the above frequency of distribution of taster gene in 180 families studied.

Table 1

Distribution of tasters and nontasters for phenylthiocarbamide in Mysore, South India

Figure 1

Pedigree of Homozygous Dominant (A), Heterozygous Dominant (B), Nontaster ♂ × Taster ♀ (C), Taster ♂ × Nontaster ♀ (D) and Homozygous Recessive (E). Shaded region represents tasters and nonshaded region represents nontasters. Roman number in the left side of the figure indicates the number of generations. Arabic number below the symbol denotes the number of individuals in that generation. These are the representative pedigrees of the 180 families screened.

Table 2

Inheritance pattern of taster gene in 180 families

Figure 2

Frequency of distribution of taster gene in 180 families in four different genotypic categories - A=TT (t) ♂ × TT (t) ♀, B = TT(t) ♂ × tt ♀, C = tt ♂ × TT(t) ♀, D = tt ♂ ♂ × tt ♀

When one of the parents was a nontaster, the frequency of tasters and nontasters in the progeny varies. By analyzing the taster phenotype of the progeny in the above 86 families, 15 and 12 families had homozygous taster father and mother respectively [Table 3]. The remaining 59 families, that is, heterozygous father or mother for taster gene with nontaster partners (test cross) had taster and nontaster progenies in the ratio 1.0: 1.54. This indicates the deviation in the segregation pattern with increased variable penetrance of nontaster allele [Figure 3] in these families.

Table 3

Segregation of homozygous and heterozygous taster gene in 86 families based on the progeny data

Figure 3

Presence of homozygous and heterozygous taster gene in 86 families studied with the genotypic categories - A=TT × tt and B = Tt × tt. In the category A all the individuals were tasters and in category B tasters and nontasters were in the frequency of 53% and 82% respectively.

Discussion

Substantial variation in taste sensitivity exists along with great degree of sequence diversity and variation in bitter taste receptor genes.[215] Wooding et al[16] have examined patterns of DNA sequence variation in the PTC gene of different populations, which accounts for up to 85% of phenotypic variance in the taster trait. They found excess of intermediate-frequency variants than neutral variants and suggested that this variation is due to the balance natural selection, which has acted to maintain “taster” and “nontaster” alleles of the PTC gene. However, the frequency of tasters in different populations as available in the literature indicates that Papago Indians in Arizona shows the highest incidence of tasters (98.6%), while Kondhs population in Orissa, India has shown only 35% of tasters.[1217] Studies in other regions showed the frequency of tasters ranged in between the two extreme cases [Table 4] indicating the wide range of variations found in the frequency of taster and nontaster genotypes. The ability to taste PTC shows complex inheritance in humans.[12] Using quantitative trait locus mapping techniques, Kim et al[2] have found a gene that accounts for 55-85% of the variance in PTC taste sensitivity.

Table 4

Frequency of tasters in world populations

In the present study, the frequency of PTC tasters is greater than nontasters. This is more evident in the unbiased category than the religious groups. However, based on the segregation analysis of heterozygous families, nontaster alleles are increased in their progeny. Since variable penetrance is more common in autosomal dominant condition and deviation in segregation pattern may be due to variable penetrance of taster allele, as heterozygotes cannot be identified. The other possibility that some of the TT × tt marriages may be infact Tt × tt, cannot be ruled out, which may be the reason for deviation in the segregation of taster and nontaster progeny.

Another possibility of the change in the genetic ratio of the PTC taster allele in heterozygotes could be due to inbreeding. The religious groups in India particularly in South India exhibit high level of second degree consanguinity.[1819] The inbreeding within these religious groups for several generations and selection of preferentially segregated nontaster allele to the subsequent generations cannot be ruled out. On the other hand, although PTC itself has not been found in nature, the ability to taste PTC is correlated strongly with the ability to taste other naturally occurring bitter substances, many of which are toxic.[2021] Therefore, understanding the nature of the variation in bitter taste and its relationship to diet and other behaviors may have important implications on human health.