Evolutionary relationships of the Tas2r receptor gene families in mouse and human

Abstract

The early molecular events in the perception of bitter taste start with the binding of specific water-soluble molecules to G protein-coupled receptors (GPCRs) encoded by the Tas2r family of taste receptor genes. The identification of the complete TAS2R receptor family repertoire in mouse and a comparative study of the Tas2r gene families in mouse and human might help to better understand bitter taste perception. We have identified, cloned, and characterized 13 new mouse Tas2r sequences, 9 of which encode putative functional bitter taste receptors. The encoded proteins are between 293 and 333 amino acids long and share between 18% and 54% sequence identity with other mouse TAS2R proteins. Including the 13 sequences identified, the mouse Tas2r family contains approximately 30% more genes and 60% fewer pseudogenes than the human TAS2R family. Sequence and phylogenetic analyses of the proteins encoded by all mouse and human Tas2r genes indicate that TAS2R proteins present a lower degree of sequence conservation in mouse than in human and suggest a classification in five groups that may reflect a specialization in their functional activity to detect bitter compounds. Tas2r genes are organized in clusters in both mouse and human genomes, and an analysis of these clusters and phylogenetic analyses indicates that the five TAS2R protein groups were present prior to the divergence of the primate and rodent lineages. However, differences in subsequent evolutionary processes, including local duplications, interchromosomal duplications, divergence, and deletions, gave rise to species-specific sequences and shaped the diversity of the current TAS2R receptor families during mouse and human evolution.

Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans

“…As noted previously (22,23), mouse and human bitter taste receptors do not form separate clusters, but rather they intermingle, indicating that ancestral receptor genes existed prior to the divergence of the primate and rodent lineages. Recently, a comprehensive phylogenetic analysis of the bitter taste receptor repertoires in the mammalian superorder Eurarchontoglires, which includes primates and rodents, revealed the existence of 19 one-to-one orthologs among the Tas2r genes of Euarchonta (including primates) and Glires (including rodents) as well as seven clusters of lineage-specific expansions (56), findings that confirm and expand previous observations (22,23). By reason of pseudogenization in either of the grand orders (e.g.…”

“…The human genome not only contains fewer intact TAS2R genes than the mouse genome but also a larger number of pseudogenes (11 in human versus 7 in mice). This has been interpreted as a sign of relaxed selective constraints on the human TAS2R gene repertoire (22). The Tas2r genes of human and mouse occur clustered at few syntenic chromosomal regions (6,22,23).…”

“…This has been interpreted as a sign of relaxed selective constraints on the human TAS2R gene repertoire (22). The Tas2r genes of human and mouse occur clustered at few syntenic chromosomal regions (6,22,23). The majority of bitter taste receptor genes located on human chromosome 12 and mouse chromosome 6, respectively, occur in clusters of species-specific bitter taste receptor genes, which likely arose from gene duplications after the divergence of primate and rodent lineages.…”

Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates

“…Interestingly, when T1R3 is combined with T1R2, it functions as a sweet taste receptor. In contrast to T1R genes, humans and mice have about 30 T2R genes (Conte et al 2003;Shi et al 2003). This might be due to the importance of the ability of bitter taste perception, which enables animals to avoid ingesting potentially toxic and harmful substances.…”

Extraordinary Diversity of Chemosensory Receptor Gene Repertoires Among Vertebrates

“…In 2000, the T2R gene family (also known as TRBs or Tas2Rs) was identified and two mouse T2R genes were shown to be bitter taste receptors Chandrashekar et al 2000 ;Matsunami et al 2000) . To date, the complete T2R gene repertoires have been described in mammals, birds, amphibians, and some fishes (Conte et al 2002(Conte et al , 2003Go 2006 ;Shi and Zhang 2006) . In addition, a small number of T2R genes have also been described in several nonhuman primates (Parry et al 2004 ;Wang et al 2004 ;Fischer et al 2005 ;Go et al 2005) .…”