New insight into the molecular determinants of function, diversity and
evolution of sweet taste receptors T1R2/T1R3 in primates
Abstract
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.