Academic journal article Genetics

Lineage-Specific Loss of Function of Bitter Taste Receptor Genes in Humans and Nonhuman Primates

Academic journal article Genetics

Lineage-Specific Loss of Function of Bitter Taste Receptor Genes in Humans and Nonhuman Primates

Article excerpt

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.

NO doubt, organisms have increasingly acquired new genes by tandem duplication and/or polyploidization (OHNO 1970). However, as evolution has proceeded, loss of genes has also occurred whenever they became dispensable under certain circumstances of interplay between genes and their environments. In animals, nutrition that is ingested daily from surroundings must have been one of the most important environmental factors and must have permitted genes involved in vitamin C biosynthesis (NiSHiKiMi et al 1994) and essential amino acid biosynthesis (LEHNINGER 1996) to be nonfunctional. A similar phenomenon may be found in genes for the sense of taste since tasting plays a crucial role in providing animals with information about proper assessments of foods and appropriate behaviors. Mammals can basically sense tastes of sweet, sour, bitterness, salt, and umami (the taste of monosodium glutamate). Of these five modalities, sweet, bitter, and umami substances are perceived by G-protein-coupled receptor (GPCR) signaling pathways (WONG et al. 1996). Two GPCR families are involved in these pathways: One is TlR, which is associated with sweet and umami substances (NELSON et al 2001; Li et al 2002), and the other is T2R, which is associated with bitter substances (ADLER et al. 2000; CHANDRASHEKAR et al. 2000; MATSUNAMI et al. 2000). Unfortunately, however, the correspondence between bitter substances (ligands) and receptors is poorly known. One exception is one of the human T2R genes, which is proven to be responsible for perception of phenylthiocarbamide (KiM et al. 2003).

Both T1R and T2R have seven transmembrane domains as a common character of GPCRs. Despite this structural similarity, these two molecules exhibit no obvious amino acid sequence similarities. Rather, TlR and T2R are closely related to the pheromone receptors V2R and VlR, respectively (MATSUNAMI and AMREIN 2003). T2R genes form a larger multigene family than TlR genes. In contrast to the presence of only 3 TlR genes in the mammalian genome (NELSON et al. 2001; Li et al. 2002), >30 T2R genes exist (CONTE et al. 2003; SHI et al. 2003). The recent chicken genome project (HiLLIER et al. 2004) ascertained that the T2Rgene repertoire had expanded in the ancestral mammalian lineage after its divergence from reptiles/birds and that the capacity for sensing bitter substances has broadened in mammals relative to chickens, which possess only 3 T2R genes. Between mammalian orders such as humans and mice, the orthologous relationships of T2R genes are found to be either one to one or one to multiple ( CONTE et al. 2003; SHI et al 2003). Since the one-to-multiple orthology has resulted from lineage-specific gene duplication, the T2R gene family has continuously undergone gene duplication even after the mammalian radiation. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.