The Repertoire Of G-Protein-Coupled Receptors In Xenopus Tropicalis

The G-Protein-Coupled Receptor(GPCR) superfamily represents the largest protein family in the human genome.These proteins transduce outside signals to intracellular effectors and play a central role in almost all physiological functions.The disruption of their normal activities in humans results in a wide variety of diseases and disorders,which gives them well-recognized roles in clinical medicine.The evolutionary data for GPCRs can be applied to further functional analyses and are particularly useful for structural evaluation of disease-causing mutations. Although the overall repertoires of GPCRs have been documented in teleost fish and mammals,no such report yet exists for amphibians.Amphibians have adapted to both aquatic and terrestrial environments,and they occupy a useful transitional state from an evolutionary perspective.The repertoire of amphibian GPCRs may help link the GPCR evolutionary history in vertebrates from teleost fish to mammals.In addition, because of their common physiological traits with all vertebrates,amphibians can be ideal non-mammalian models for GPCR-related functional and medical research.For this purpose,the western clawed frog Xenopus(Silurana) tropicalis,which is a suitable model for physiology and biomedical research,was chosen for investigation. A strategy was presented for detecting and identifying GPCR genes from a genomic assembly.The findings are the followings.(1) We have identified 1452 GPCRs in the X.tropicalis genome.(2) Phylogenetic analyses classified these receptors into seven families, consisting of Glutamate,Rhodopsin,Adhesion,Frizzled,Secretin,Taste 2 and Vomeronasal 1. (3) X.tropicalis shares a more similar repertoire of GPCRs with mammals than it does with fish.(4) Nearly 70%of X.tropicalis GPCRs are represented by three types of receptors thought to receive chemosensory information from the outside world: olfactory,vomeronasal 1 and vomeronasal 2 receptors.(5) The repertoires of chemosensory related receptors are shaped by lineage specific expansions which demanded by functional innovation or are simply the results of lower selective constraints.By comparing X.tropicalis receptor groups with those of mammals and/or fish, we performed detailed phylogenetic analyses.These comparative data provide information about the evolutionary history of GPCRs,and the available receptor sequences may help to identify conserved sequence motifs that are responsible for certain aspects of GPCR functionality,especially those which may cause disease through mutation.The availability of the repertoire of X.tropicalis GPCRs can yield insights into the physiological functions of GPCRs and furthermore,the identified X. tropicalis orphan GPCRs may offer useful information in the search for novel therapeutic agents.