Molecular evolution of a chordate specific family of G protein-coupled receptors

Abstract

BackgroundChordate evolution is a history of innovations that is marked by physical and behavioral specializations, which led to the development of a variety of forms from a single ancestral group. Among other important characteristics, vertebrates obtained a well developed brain, anterior sensory structures, a closed circulatory system and gills or lungs as blood oxygenation systems. The duplication of pre-existing genes had profound evolutionary implications for the developmental complexity in vertebrates, since mutations modifying the function of a duplicated protein can lead to novel functions, improving the evolutionary success.ResultsWe analyzed here the evolution of the GPRC5 family of G protein-coupled receptors by comprehensive similarity searches and found that the receptors are only present in chordates and that the size of the receptor family expanded, likely due to genome duplication events in the early history of vertebrate evolution. We propose that a single GPRC5 receptor coding gene originated in a stem chordate ancestor and gave rise by duplication events to a gene family comprising three receptor types (GPRC5A-C) in vertebrates, and a fourth homologue present only in mammals (GPRC5D). Additional duplications of GPRC5B and GPRC5C sequences occurred in teleost fishes. The finding that the expression patterns of the receptors are evolutionarily conserved indicates an important biological function of these receptors. Moreover, we found that expression of GPRC5B is regulated by vitamin A in vivo, confirming previous findings that linked receptor expression to retinoic acid levels in tumor cell lines and strengthening the link between the receptor expression and the development of a complex nervous system in chordates, known to be dependent on retinoic acid signaling.ConclusionsGPRC5 receptors, a class of G protein-coupled receptors with unique sequence characteristics, may represent a molecular novelty that helped non-chordates to become chordates.

A brief review on the evolution of GPCR: conservation and diversification

“…The ancestor of metabotropic glutamate receptor was proposed to be found in slime molds and sponges [35]. By means of mining GPCR evolutionary data from fossils, Torsten Schoneberg provided several clues that the phylogenetically oldest GPCR might include fungal pheromone receptors, cAMP and glutamate-receptor-like receptors [10][11][12]. A schematic presentation of GPCR evolution superfamily shows that adhesion and frizzled as well as large rhodopsin family are children of the cAMP.…”

“…Studies on GPCR evolution have been done in several eukaryotic species, which provide insights from different perspectives [5][6][7][8][9][10][11][12]. However, our understanding of GPCR evolution is merely based on extant genome sequences since most ancient eukaryotic species ever lived on earth are extinct.…”

Association between genetic variants in the promoter region of a novel antisense long noncoding RNA RP11‐392P7.6 and colorectal cancer risk

“…GPRC5D, one of the integral components of cell membrane, could get involved in transduction and regulation of signaling pathways [Harada et al, 2007;Howard et al, 2001]. It may play an important role in lots of physiological processes such as embryogenesis and differentiation [Kurtenbach et al, 2011]. Besides, previous studies have suggested that GPRC5D could refer to the progression of many cancers [Cohen et al, 2013;Wolf et al, 2014].…”

“…However, the number of antisense lncRNAs which have been functionally characterized in CRC are quite limited [Nakano et al, 2006]. G-protein-coupled receptor family C, group 5, member D (GPRC5D) is an integral mediator of extracellular signal transduction pathways [Harada et al, 2007;Kurtenbach et al, 2011]. It could be a promising marker for monitoring tumor load, for its aberrant expression has been previously found in some kinds of cancers [Atamaniuk et al, 2012;Cohen et al, 2013].…”

A Crucial Role of the RGS Domain in Trans-Golgi Network Export of AtRGS1 in the Protein Secretory Pathway

“…These two cysteine residues are conserved in AtRGS1 orthologs in plants but not in fungi (Johnston et al, 2007), indicating that their role in protein expression is limited to the plant kingdom. In animals, a pair of cysteine residues similar to AtRGS1 is found in the short N-terminus of the GPCR5 family (Kurtenbach et al, 2011). It remains unclear whether they are involved in receptor exit from the ER.…”