Probing the Evolutionary History of Human Bitter Taste Receptor Pseudogenes by Restoring Their Function

Lineage-specific gene losses can be driven by selection or environmental adaptations. However, a lack of studies on the original function of species-specific pseudogenes leaves a gap in our understanding of their role in evolutionary histories. Pseudogenes are of particular relevance for taste perception genes, which encode for receptors that confer the ability to both identify nutritionally valuable substances and avoid potentially harmful substances. To explore the role of bitter taste pseudogenization events in human origins, we restored the open reading frames of the three human-specific pseudogenes and synthesized the reconstructed functional hTAS2R2, hTAS2R62 and hTAS2R64 receptors. We have identified ligands that differentially activate the human and chimpanzee forms of these receptors and several other human functional TAS2Rs. We show that these receptors are narrowly tuned, suggesting that bitter-taste sensitivities evolved independently in different species, and that these pseudogenization events occurred because of functional redundancy. The restoration of function of lineage-specific pseudogenes can aid in the reconstruction of their evolutionary history, and in understanding the forces that led to their pseudogenization.