Bitter taste receptors: Genes, evolution and health

Abstract

Bitter taste perception plays vital roles in animal behavior and fitness. By signaling the presence of toxins in foods, particularly noxious defense compounds found in plants, it enables animals to avoid exposure. In vertebrates, bitter perception is initiated by TAS2Rs, a family of G protein-coupled receptors expressed on the surface of taste buds. There, oriented toward the interior of the mouth, they monitor the contents of foods, drinks and other substances as they are ingested. When bitter compounds are encountered, TAS2Rs respond by triggering neural pathways leading to sensation. The importance of this role placed TAS2Rs under selective pressures in the course of their evolution, leaving signatures in patterns of gene gain and loss, sequence polymorphism, and population structure consistent with vertebrates' diverse feeding ecologies. The protective value of bitter taste is reduced in modern humans because contemporary food supplies are safe and abundant. However, this is not always the case. Some crops, particularly in the developing world, retain surprisingly high toxicity and bitterness remains an important measure of safety. Bitter perception also shapes health through its influence on preference driven behaviors such as diet choice, alcohol intake and tobacco use. Further, allelic variation in TAS2Rs is extensive, leading to individual differences in taste sensitivity that drive these behaviors, shaping susceptibility to disease. Thus, bitter taste perception occupies a critical intersection between ancient evolutionary processes and modern human health.

Keywords: bitter; diet; genetics; molecular evolution; senses; taste.

Figure 1.

The Death of Socrates, by Jacques-Louis David (1787). Several lines of evidence suggest that Socrates was executed using extracts of hemlock (Conium maculatum) containing coniine and related alkaloids. Descriptions of Socrates's symptoms as he died to raise the possibility that additional compounds were included in the mixture but their identities remain unknown [5]

Figure 2.

Tongue anatomy. Taste receptor cells are clustered in bundles beneath the surface of papillae, where they are exposed to the interior of the mouth through pores. TAS2Rs in the apical portion of the cells are poised to detect compounds in foods, smoke, pharmaceuticals and other ingested substances (©Casey Henley, CC BY-NC-SA 4.0 International License)

Figure 3.

Bitter taste transduction cascade. TAS2Rs initiate the transduction process when exposed to compatible compounds. These interactions determine which substances are perceived as bitter and which are not, placing TAS2Rs under selective pressures that vary according to diet

Figure 4.

Example interactions between TAS2Rs and plant secondary compounds described by Meyerhof et al. [63]. Filled circles indicate activation, empty circles indicate no activation. Two key patterns are that most TAS2Rs are responsive to multiple compounds, and many compounds activate multiple TAS2Rs. These patterns extend across the TAS2R family in humans

Figure 5.

Size of bitter taste receptor gene repertoires in bony fish, amphibia, reptilia, aves and mammalia. Gene count is proportional to image height. Across species studied to date, the number ranges from 0 (in some marine mammals and birds) to 136 (in frogs). The large number of TAS2Rs in frogs may be due to their dietary reliance on insects, which often sequester secondary metabolites from consumed plants

Figure 6.

Intact genes and pseudogenes in primates. All primates studied to date harbor both intact genes and pseudogenes. However, their numbers vary even across closely related taxa, such as humans and chimpanzees. This suggests that gene birth–death processes are an important mechanism of adaptation to toxin exposure. Redrawn from Ref. [79]

Figure 7.

Cassava toxicity and konzo. (A) Konzo patients in the Democratic Republic of Congo. Note foot position of child and crutch used by an adult. Photograph courtesy of Dr Thorkild Tylleskär, University of Bergen. (B) Plot of cyanogenic glucoside content and perceived bitterness of samples tasted by farmers in Malawi. Higher taste score indicates higher perceived bitterness. Redrawn from Ref. [112]