Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005 May;170(1):313-26.
doi: 10.1534/genetics.104.037523. Epub 2005 Mar 2.

Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates

Yasuhiro Go  1 , Yoko Satta, Osamu Takenaka, Naoyuki Takahata
Affiliations

Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates

Yasuhiro Go et al. Genetics. 2005 May.

Abstract

Since the process of becoming dead genes or pseudogenes (pseudogenization) is irreversible and can occur rather rapidly under certain environmental circumstances, it is one plausible determinant for characterizing species specificity. To test this evolutionary hypothesis, we analyzed the tempo and mode of duplication and pseudogenization of bitter taste receptor (T2R) genes in humans as well as in 12 nonhuman primates. The results show that primates have accumulated more pseudogenes than mice after their separation from the common ancestor and that lineage-specific pseudogenization becomes more conspicuous in humans than in nonhuman primates. Although positive selection has operated on some amino acids in extracellular domains, functional constraints against T2R genes are more relaxed in primates than in mice and this trend has culminated in the rapid deterioration of the bitter-tasting capability in humans. Since T2R molecules play an important role in avoiding generally bitter toxic and harmful substances, substantial modification of the T2R gene repertoire is likely to reflect different responses to changes in the environment and to result from species-specific food preference during primate evolution.

PubMed Disclaimer

Figures

F<sc>igure</sc> 1.—
Figure 1.—
Phylogenetic tree of bitter taste receptor (T2R) genes based on amino acid sequences. Genes in humans and mice are shown as solid and shaded, respectively. The tree was reconstructed by the NJ method (Saitou and Nei 1987) on the basis of the p distances, and only >50% bootstrap values are shown at each node (1000 replications). Pseudogenes in this study are defined by the presence of ORF disruptive mutations and are indicated by asterisks (*). The codon frames in pseudogenes are inferred from those of closely related functional genes. The nomenclature of human T2R genes is the same as that in Conte et al. (2002) and Shi et al. (2003). However, because of the different designation systems of the mouse genes used by two research groups (Conte et al. 2002, 2003; Shi et al. 2003), we have renamed the mouse genes. Detailed nomenclatures in humans and mice are in Table 1. The numbers in parentheses stand for those of nonsense and indel mutations, respectively. The definitions of categories A, B, and C are given in the text.
F<sc>igure</sc> 2.—
Figure 2.—
Phylogenetic tree of 305 T2R genes based on amino acid sequences in primates and mice. Genes used are from hominoids (blue), OWMs (red), NWMs (green), prosimians (yellow), tupais (gray), and mice (black). The NJ tree is reconstructed by using the p distances. The numbers in boldface type correspond to those in the locus designation system for human T2R genes. Pseudogenes are indicated by asterisks (*). Nonsense (red crosses) and indel (blue crosses) mutations responsible for pseudogenization are placed along branches. The definitions of categories A, B, and C are the same as in Figure 1.
F<sc>igure</sc> 3.—
Figure 3.—
Partial alignments of the nucleotide sequences of primate T2R genes. Dots show the same nucleotides as those in the top sequence, which were retrieved from GenBank. Both asterisks and shaded boxes show the location of mutations that impair intact ORFs. (A) T2R62 is pseudogenized by two nonsense mutations (CAG → TAG at codon position 235 and GAA → TAA at 292). (B) T2R2 is polymorphic in terms of a two-base deletion at codon position 160 in human populations. Only Adygei (from Eastern Europe), Biaka, and Mbuti Pygmies (both from Africa) possess the intact genes, while the deletion is found in all sequences collected from 10 other human populations (Karitiana, Surui, Waorani Indians from South America, Russians from Eastern Europe, Druze from the Middle East, Atayal, Chinese, Japanese from Eastern Asia, and Khmers and Melanesians from Southeast Asia) and from GenBank resources. (C) T2R64 is a human-specific pseudogene (TGG → TGA at 280). This gene also became a pseudogene in the orangutan through an independent nonsense mutation (TGG → TGA at 49). (D) Independent mutations disrupt T2R55 in the four apes: chimpanzees (five-base deletion at 172–173), gorillas (one-base insertion at 271), orangutans (one-base deletion at 303), and gibbons (two-base deletion at 103); in the prosimians: ring-tailed lemurs (two one-base deletions at 43 and 227, two-base deletion at 116, one-base insertion at 271, and two nonsense mutations at 90 and 236); and in the tupai: common tree shrews (one-base insertion at 66).
F<sc>igure</sc> 4.—
Figure 4.—
The rate of pseudogenization in humans and nonhuman anthropoidea. Each cross on a terminal branch shows species-specific pseudogenization. The divergence times (MY) represented above each branch are from Goodman et al. (1998). While three human-specific pseudogenes have arisen within 6 MY, 15 (1 + 2 + 2 + 2 + 2 + 3 + 2 + 1) pseudogenes in nonhuman anthropoidea have accumulated within 117 MY (6 + 7 + 14 + 18 + 14 + 14 + 22 + 22). Pseudogenization that occurred along internodal branches (dashed lines) is excluded from consideration.
F<sc>igure</sc> 5.—
Figure 5.—
The extent of positive and negative selection on individual codons. Schematic positions of three functional domains of the T2R gene (ECs, TMs, and ICs) are shown on the x-axis. The value above and below the x-axis, respectively, indicates an excess and deficiency in the number of per-site nonsynonymous substitutions (dN) over per-site synonymous ones (dS) in an individual codon. The zero value means dN = dS. Asterisks (*) show significant positive selection (P < 0.05) based on the extended binominal distribution (http://www.datamonkey.org/).
F<sc>igure</sc> 6.—
Figure 6.—
The bS and bN values of category A genes (▵) and category C genes (•) in ECs (top) and TMs + ICs (bottom). The x- and y-axis stand for bS and bN, respectively. The primate genes used for category A are T2R15, T2R43-44, T2R45, T2R46, T2R47, T2R48, T2R49, T2R50, and T2R55, and those for category C are T2R1, T2R2, T2R3, T2R4, T2R7, T2R16, T2R38, T2R39, T2R40, T2R41, T2R56, and T2R62.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Adler, E., M. A. Hoon, K. L. Mueller, J. Chandrashekar, N. J. Ryba et al., 2000. A novel family of mammalian taste receptors. Cell 100: 693–702. - PubMed
    1. Chandrashekar, J., K. L. Mueller, M. A. Hoon, E. Adler, L. Feng et al., 2000. T2Rs function as bitter taste receptors. Cell 100: 703–711. - PubMed
    1. Conte, C., M. Ebeling, A. Marcuz, P. Nef and P. J. Andres-Barquin, 2002. Identification and characterization of human taste receptor genes belonging to the TAS2R family. Cytogenet. Genome Res. 98: 45–53. - PubMed
    1. Conte, C., M. Ebeling, A. Marcuz, P. Nef and P. J. Andres-Barquin, 2003. Evolutionary relationships of the Tas2r receptor gene families in mouse and human. Physiol. Genomics 14: 73–82. - PubMed
    1. Fischer, A., Y. Gilad, O. Man and S. Pääbo, 2005. Evolution of bitter taste receptors in humans and apes. Mol. Biol. Evol. 22: 432–436. - PubMed

Publication types

Substances

Associated data