The ability to taste bitterness may help us avoid poisoning from eating toxixc plants. Animals in general, and our ancestors, the primates developed this trait. The PTC gene is responsible for our perception of bitter taste.
All nonhuman primates have only one variant of the PTC gene known as PAV, which is therefore considered as the ancestral or original gene form, these apes are homozygous for it (meaning that the two copies they carry, one from each parent, are identical). This is known as the "taster" allele, it allows them to taste bitterness.
Genetics
PTC bitter gene, is formally known as the TAS2R38 gene. It comes in eight different variants but two of them are prevalent, the ancestral "taster" allele, and a "non-taster" allele which comprise 96% of the human population. These encode a specific protein, which contains 333 aminoacids, the 7-transmembrane domain G-protein-coupled receptor which responds to bitterness.
The different alleles cause tiny variations in the position of some aminoacids in this protein and cause the "taster" and "non-taster" variants and four other intermedieate "less-taster" types.
The variants are named after the positions of these amino acids the "original" or "ancestral" form is the PAV form (because it contains proline at position 49, alanine at position 262, and valine at position 296), this is the "taster" form.
Neanderthals and Denisovans are also PAV tasters (Source).
The second mayor form is the "non-taster" one, known as AVI, because it contains alanine, valine and isoleucine aminoacids in those three positions, respectively.
Further down we will look into why do the "non-taster" alleles survive, and account for roughly half of the human population, who can't taste bitter flavors. If tasting bitterness protects against plant toxins, why do so many of us carry the non-taster variant?
The other six variants are AAV, AVV, AAI, PAI, PVI, AAI, and PVV and are found at relatively low frequencies.
The prevalence found in one study was the following: 42.3% PAV (ancestral, taster), 53.1% (derived, non-taster) and the intermediate taster ones (2.5% AAV, 1.2% AAI, 0.8% PAI, and 0.1% PVI, no AVV or PVV were detected). (Source).
People who inherited at least one copy of the PAV allele from their parents are able to taste bitterness.
These alleles also have a geographic distribution, PAV and AVI are the most frequent, and make up the vast majority of European and Asian alleles. They are also found in Africa, but there, AAI is found at a relatively high frequency. The table below, (Table 1 from Risso, D., Mezzavilla, M., Pagani, L. et al. (2016) Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal. Sci Rep 6, 25506), shows data from 5,589 individuals sampled across 105 populations around the World, and it highlights the slight variations in different populations.
The "Americans" in the table shown in the image are from the following groups (the number is the individuals in each sample): North America Maya Mexico 42, North America Puerto Ricans Puerto Rico 110, South America Colombians Colombia 134, South America Karitiana Brazil 28, South America Mexicans Mexico 160, South America PEL Peru 170, and South America Surui Brazil 16.
American Natives and Bitter Taste Genes
Looking at the data, we see that PVV is exclusively European, and does not appear in any other population, including Amerindians. It didn't admix into them despite the large-scale intermingling that took place after 1492, which is quite surprising.
AAI is definitively African where it reaches 13.22%, and in small amounts among Europeans and Americans (perhaps due to African genetic mixing into Southern Europeans and slave trade into America).
PVI is extremely rare, and is found at higher frequencies among Native Americans, with 0.19%, followed by Africans by 0.15%. None in Asia, and only 0.03% in Europe. We could suppose that African slave trade brought it into America, but why is the prevalence 26.6% higher in the Americas than in Africa? Being absent in Asia it surely didn't arrive via Beringian migrants.
AAV, absent in Asians is also found among Americans (2.26%), slightly lower than Europeans (3.56%) and much higher than Africans (0.61%). If it introgressed into Amerindians through Europeans, then, why didn't the European AVI do so in a similar proportion? (AVI among Americans is 26.69% while it is 49.22% among Europeans and roughly 33% in Africans and Asians).
Regarding the ancestral PAV, original allele, it is highest among Native Americans with 68.8%. The other populations have a lower frequency of it.
Interestingly, according to Kim et al. (See: Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D., Science. 2003 Feb 21;299(5610):1221-5. doi: 10.1126/science.1080190. PMID: 12595690. Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide), "The common nontaster AVI haplotype was observed in all populations except Southwest Native Americans, who were exclusively homozygous for the PAV haplotype" (these natvies were almost 100% tasters).
Another article (Flores SV, Roco-Videla A, Aguilera-Eguía R. Variation in haplotype frequencies of the TAS2R38 gene, associated with the perception of bitter taste. Salud, Ciencia y Tecnología. 2025 Jan. 1;5:1026.) notes taster prevalence among Peruvian Andean people: "A particularly interesting case is the Peruvian population, which stands out for its high frequency of bitter taste perception diplotypes. In this population, only 1 % has the AVI/AVI diplotype, indicating an almost total prevalence of bitter taste perception (PAV/PAV and PAV/AVI). This exception suggests a specific dietary adaptation in the Andean region, or well the result of genetic drift."
Why hasn't natural selection erased the non-taster alleles?
For human beings, nearly all naturally occurring plant toxins poisons taste bitter. But, not all bitter tasting foods are poisonous. Many bitter tasting foods are harmless.
One interesting paper suggests that excluding all bitter flavored plants would mean lost calories and nutrients, because many bitter veggies are healthy and have no harmful effect (citric fruits, bitter melon, or kale, as well as the other cruciferous vegetables), some foods like beer, green tea, or coffee are bitter yet pleasurable. Also, bitterness may also mean medical properties such as quinine (the bitter ingredient of tonic water) used to combat malaria, or the pain-killing properties of salicin, found in willow leaves, on which the aspirin was based.
Humans also have cognition, and curiosity, they may try a bitter food, which if it doesn't cause harm, can then be safely added to the diet.
A paper (T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection Robert J. Lee,… , Danielle R. Reed, Noam A. Cohen. Published October 8, 2012. Citation Information: J Clin Invest. 2012;122(11):4145-4159. https://doi.org/10.1172/JCI64240.) found that bitter taste receptors also act upon the tissue lining the upper respiratory tract, and those carrying at both PAV alleles (tasters) are better protected from microbes than those carrying one or none: "these individuals are more likely to be infected with gram-negative bacteria such as P. aeruginosa than those with 2 functional receptor alleles." It also suggests that " humans with more non-taster alleles live in the colder climates, where the evolutionary pressure for the taster genotype may be relaxed, as there are fewer pathogens than in warmer climates."
But why the AVI non-taster allele is still carried at around 50% levels in humans. Could it be functional for other reasons and offer an evolutionary advantage that we have not yet identified?
A 2012 paper (Campbell MC, Ranciaro A, Froment A, Hirbo J, Omar S, Bodo JM, Nyambo T, Lema G, Zinshteyn D, Drayna D, Breslin PA, Tishkoff SA. Evolution of functionally diverse alleles associated with PTC bitter taste sensitivity in Africa. Mol Biol Evol. 2012 Apr;29(4):1141-53. doi: 10.1093/molbev/msr293. Epub 2011 Nov 29. PMID: 22130969; PMCID: PMC3341826) says it does, but isn't yet fully understood:
"the selective force maintaining common AAV, AAI, and AVI haplotypes for extraordinarily long periods of time remains unclear. Although both AAV and AAI are associated with intermediate bitter taste sensitivity, the AAI haplotype is more common in Africa than AAV. Intriguingly, the AAV haplotype may represent a “stepping stone” to other more advantageous haplotype variation, such as AAI and AVI. We suggest that common PAV, AAI, and AVI haplotype variation may be maintained at high frequencies in response to selective pressures unrelated to diet. Indeed, recent studies have shown that bitter taste receptors are expressed in a variety of cell types in the human gastrointestinal tract (Rozengurt and Sternini 2007) and lungs (Shah et al. 2009; Deshpande et al. 2010), where they influence insulin and glucose levels (Dotson et al. 2008), eliminate harmful inhaled substances (Shah et al. 2009), and stimulate the relaxation of airways for improved breathing (Deshpande et al. 2010). These studies demonstrate that bitter taste loci have a number of different functions and raise the possibility that common variants at TAS2R38 may be under selection due to their physiological roles in human health beyond oral gustatory function. Though we cannot conclusively distinguish the selective forces maintaining common variation at TAS2R38, it is clear that genetic variation at this locus is diverse and has been functionally important long before modern Homo sapiens existed."
Neanderthals
Our relatives, the Neanderthals had bitter taste perception (source) the El Sidrón individual, was heterozygous, carrying the ancestral PAV and the derived allele with an alanine in position 49, the study didn't clarify the other two positions, so this Neanderthal could have carried the common non-taster AVI, or the more rare variants AAI or AAV.
This means that the non-taster variant dates to before humans and Neanderthals split around 500,000 years ago. Of course, genetic flow between both groups could have introduced the derived non-taster variant into the 48,000-year-old Sidrón individual (meaning it originated among our H. sapiens), but the study considers this unlikely and affirms that "our results indicate that the non-taster alleles were already present in the ancestral human populations from which both Neanderthals and modern humans diverged."
The rise of non-tasters took place long ago. Studying African populations Tishkoff et al. (2012) found the following evolution and timeline for this gene from the PVA to the AVI form:
The PAV → AAV variant arose when P was replaced by A at site 49 1.3 million ± 242,211 years ago. Then the AAV → AAI shift took place when V was replaced with I at position 296, 1.0 million ± 267,268 years ago. These changes predate the split between Neanderthal-Denisovans and our ancestral H. sapiens lineage. Another mutation was the A for V at position 262, causing the AAI → AVI shift. This one took place 336,000 ± 89,845 years ago. The other low-frequency alleles are much younger than 200,000 years. Below is and years old, respectively. The lower frequency variants, including those that are associated with decreased PTC sensitivity, appear to be much younger in age, occurring within the last 200,000 years. Below is Fig. 4, from this paper, we added in red letters, each allele.
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