Clementine Chen

Pronouns: she/her/hers

Hometown: Jinhua, China

Fun Fact: My favorite Disney characters are Alice and the Cheshire Cat.

In the lab: joined us for the summer research program 2022 and stayed until graduating (Spring 2024).

Update: starting a Masters program in Fall 2024 in Computational Biology and Quantitative Genetics @ Harvard T.H. Chan school of Public Health.

Quantifying the evidence for adaptive evolution of the TAS2R38 bitter receptor gene in primates

Broader project: Evolution of bitter taste receptors in primates and other mammals/

Taste is a sense that allows the perception and distinction of different flavors via specialized cells in the tongue. Taste buds are in charge of forming taste perception, and type II taste receptors (TAS2R) are the gene family that codes for bitter taste receptors, which are considered G-protein coupled receptors. Combined, these receptors can bind to a large number of molecules, and each receptor has a specific affinity to different molecules. Since bitter taste is important for animals to avoid swallowing potentially harmful chemicals, we believe that the TAS2R genes that code for bitter taste receptors may have evolutionary significance to humans and other primates. Inside the protein family, there are 25 protein-coding genes and 11 pseudogenes that are found in humans.

Specifically, TASR38 is the gene that codes for taste receptor type 2 number 38, which binds to 23 known ligands. The G-protein coupled receptor is associated with the perception of taste phenylthiocarbamide (PTC), which is tasted differently by different people. The TASR38 gene is the most studied protein-coding bitter receptor gene from an evolutionary perspective. In humans, two divergent TAS2R38 haplotypes exist at intermediate frequencies, which has been interpreted as evidence that they have been maintained by balancing selection. However, a more recent study argues that the recent evolution of this gene can be explained fully by demographic events in human evolution. Does the TAS2R38 gene play a role in the adaptive evolution (positive selection and/or balancing selection) of humans and other primates? We hypothesize that specific binding sites in this gene may have been subjected to adaptive evolution in humans. If the hypothesis is correct, there will be an increased dN/dS value (ratio of nonsynonymous substitution rate to synonymous substitution rate) at certain binding sites of the gene, corresponding to those that determine ligand specificity. Although this gene can be found in most mammals sequenced to date, we will focus on primates, since this is the taxonomic group including humans and our closest relatives. We will also test whether evidence for adaptive evolution is different for different subgroups of primates, such as the great apes (chimps, bonobos, gorillas, orangutans, humans), New World, and Old World Monkeys. Another test will also be done to detect if a specialized diet of humans and other primates affected the evolution of their TAS2R38 gene. If so, feeding habits might be a factor that determines the genetic variations of the TAS2R38 gene.

In the Bitarello lab, we will be focusing on using computational methods to conduct experiments at the level of comparative genomics. The data used will be publicly available. To find out the evolutionary relationship between species, the obtained protein-coding sequences will be aligned to create phylogenetic trees. Codon substitution models will be implemented in software PAML and HyPhy to measure the evidence for natural selection at the protein level for different groups (sites in the gene or branches in the phylogeny).

The phylogenetic analysis results may bring new insights to other scientific fields. Since taste affects food intake, knowing the ligand-binding mechanism helps drug developers understand how bitter taste forms so that they are able to create drugs with higher acceptance by patients. Also, based on a recent study, homozygous carriers of a certain variant of the TAS2R38 gene may be related to pine nut syndrome which suggests that dietary habits may be a potential factor to determine the evolution of bitter taste genes. Besides that, the evolutionary significance of the TAS2R38 bitter receptor gene promotes people’s understanding of cultural evolution in human history and how dietary preferences shape human evolution.

BMC Summer Research Program Webpage