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.
Highlights
Chordate 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
While the vast majority of G-protein coupled receptor (GPCR) have short N-termini and agonist binding sites within the seven-transmembrane (7TM) domains, family C receptors are characterized by a large extracellular amino-terminal domain of up to 600 amino acids, which has been shown to function as a ligand binding site [4]
Similarity searches showed that the four known GPRC5 receptor sequences can be found in all mammalian genomes, while additional sequences sharing higher similarities to GPRC5 receptors than to other GPCRs do not exist in mammals
Summary
Chordate 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. GPRC5 receptors are classified as members of the GPCR family C, but have a shorter N-terminus compared to the other family members. They build a subfamily with four known members GPRC5A, GPRC5B, GPRC5C, and GPRC5D, for which no specific ligands are described [5]. GPRC5D was found to be associated with hard-keratinized structures, like cortical cells of the hair shaft [12]. The role of these receptors in the tissues they are expressed in is so far unknown. We compared GPRC5 receptor sequences in all listed species, analyzed expression patterns and examined their regulation by RA
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