Congrui Wang

and 5 more

Sweet taste is a primary sensation for the preference and adaption of primates to diet, which is crucial for their survival and fitness. It is clear now that the sweet perception is mediated by a G protein-coupled receptor (GPCR)-sweet taste receptor T1R2/T1R3, and many behavioral or physiological experiments have revealed the diverse sweet taste preferences and sensitivities in primates. However, the structure-function relationship of T1R2s/T1R3s in primates, especially the molecular basis for their species-specific sweet taste, has not be well understood until now. In this study, we performed a comprehensive sequence, structural and functional analysis of sweet taste receptors in primates to elucidate the molecular determinants mediating their species-dependent sweet taste recognition. Our results indicate that distinct taxonomic distribution and classification are present in both T1R2s and T1R3s, which are demonstrated by the conservation/variation of sequences in sequence similarity networks and phylogenetic analysis. Furthermore, significant characteristics (interaction, coevolution and epistasis) for several subsets of function-related potential residues, which could partly account for the previously reported behavioral and physiological results of taste perception in primates, are also revealed. Moreover, the prosimians Lemuriformes species, which were reported to have no sensitivity to aspartame, could be proposed to be aspartame tasters based on the present analysis. This hypothesis was further validated by the cell-based functional analysis of the T1R2/T1R3 of the Lemuriformes species Coquerel’s sifaka and its two site-directed mutants. Collectively, our study provides new insights and promotes a better understanding for the diversity, function and evolution of sweet taste receptors in primates.