TAS2R1

New genetic data show that humans and sharks share bitter taste receptors, even though their evolutionary pathways separated nearly 500 million years ago. A research team from the University of Cologne, in collaboration with colleagues from the Leibniz Institute for Food Systems Biology in Freising, has discovered a receptor for bitter taste in twelve different cartilaginous fish (sharks and rays). The receptor belongs to the so-called taste receptors type 2 (T2R), which also make humans perceive bitter and potentially toxic foods. Until now, it was assumed that such receptors only occur in bony vertebrates. The work was published under the title 'A singular shark bitter taste receptor provides insights into the evolution of bitter taste perception' in the journal Proceedings of the National Academy of Sciences (PNAS). In the past, molecular research has had limited information on sharks, as their genomes are often relatively large. Therefore, sequencing is often more complex and takes longer than with many other animals. However, the techniques are more advanced nowadays, providing ever more information on the gene sequences of many cartilaginous fishes. This enabled the neurobiologists lecturer (Privatdozent) Dr Maik Behrens and Tatjana Lang from the Leibniz Institute for Food Systems Biology and Professor Dr Sigrun Korsching at the Institute of Genetics of the University of Cologne to specifically search for bitter taste receptors in cartilaginous fish. Twelve out of seventeen cartilaginous fish genomes studied contained genes for the taste receptors type 2, with only one T2R gene present in each species. The researchers named this single gene T2R1. The fact that only a single T2R gene was found suggests that it is the original form of these bitter taste receptors, which was not altered by gene duplication and subsequent different specialization of the resulting receptors. 'These findings give us new insights into the evolution of these receptors: We can look back almost 500 million years on the molecular and functional origin of an entire family of bitter taste receptors. Because that is how old the last common ancestor of cartilage and bony fish is,' says Sigrun Korsching. The authors have also introduced the T2R1 gene of the bamboo shark (C. plagiosum) and the catshark (S. canicula) into immortalized cell lines. The results showed that both sharks can taste bitter substances also perceived by humans, such as colchicine or bile acid. A screening of ninety-four human bitter substances identified eleven substances that could also activate the sharks' receptors. Some of these eleven substances also activate the bitter taste receptors of the 'living fossil' coelacanth (Latimeria chalumnae), an ancient species of bony fish, as the authors have shown in a previous study. Sigrun Korsching summarizes that 'the extent to which this function has been conserved is astonishing, i.e. through the entire evolution of vertebrates.'

Taste receptors for bitter substances are not only found on the tongue but also on cells outside the oral cavity. As a new study now shows, extraoral bitter taste receptors could also serve as endogenous sensors for bile acids. This discovery suggests that, in addition to food components, endogenous substances may have influenced the evolution of bitter taste receptors. Furthermore, the study provides new approaches to explore the health effects of food constituents in which extraoral bitter taste receptors are involved. Taste receptors for bitter substances are not only found on the tongue but also on cells outside the oral cavity. As a new study by the Leibniz Institute for Food Systems Biology at the Technical University of Munich now shows, extraoral bitter taste receptors could also serve as endogenous sensors for bile acids. This discovery suggests that, in addition to food components, endogenous substances may have influenced the evolution of bitter taste receptors. Furthermore, the study provides new approaches to explore the health effects of food constituents in which extraoral bitter taste receptors are involved. As taste sensors, bitter taste receptors serve to detect and avoid potential toxins in food. Relatively recent findings also indicate that bitter taste receptors are also found on cells of the lung, brain, and gastrointestinal tract, and on blood and sperm cells. A fact that suggests further, less well-studied receptor functions in the body, especially since the human body also produces bitter substances itself. Based on these findings, the question arises whether bitter taste receptors evolved primarily as taste receptors or rather as endogenous sensors interacting with endogenous bitter substances. The latter, of course, would require that concentrations of endogenous substances in the corresponding body fluids be sufficient to activate endogenous bitter taste receptors on extraoral tissues and cells. Bile acids are endogenous bitter substances Bile acids are a good example of endogenous bitter substances and are present in various body fluids. Therefore, a team led by Maik Behrens from the Leibniz Institute in Freising, Germany, investigated which of the approximately 25 human bitter taste receptor types respond to physiologically relevant bile acid concentrations. For this purpose, the team used an established cellular test system and combined functional experiments with molecular modeling approaches. The eight bile acids tested included primary, secondary, tertiary, and conjugated bile acids. As the team shows, five bitter taste receptor types respond to the bile acids tested. "In this context, the measured activation thresholds of the receptors matched very well the bile acid concentrations reported for human body fluids in the literature," says Florian Ziegler, a doctoral student at the Leibniz Institute who contributed significantly to the study. "Moreover, we were not only able to characterize the binding of bile acids to the bitter taste receptor TAS2R1 by modeling studies but even reproduced the differences of experimental activity data," adds Antonella Di Pizio, who heads the Molecular Modeling group at the Leibniz Institute. Bile acids activate extraoral bitter taste receptors "Our results suggest that there is indeed a physiological relationship between bile acids and certain extraoral bitter taste receptors and that the latter act as endogenous sensors of bile acid levels. They also support the hypothesis that not only external factors such as bitter food constituents have influenced the evolution of bitter taste receptors, but also endogenous ones," summarizes principal investigator Maik Behrens. However, further studies are urgently needed to clarify the exact biological functions of the extraoral receptors, the biologist continues. He adds: "Gaining a deeper understanding of these functions could provide valuable insights into the potential health effects of food components when they interact with the extraoral bitter taste receptor ligand systems."