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Open Access Highly Accessed Research article

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

Stefan Kurtenbach1, Christoph Mayer2, Thomas Pelz3, Hanns Hatt1, Florian Leese4 and Eva M Neuhaus35*

Author Affiliations

1 Department of Cell Physiology, Ruhr University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany

2 Zoologisches Forschungsmuseum Alexander Koenig, Adenauerallee 160-163, 53113 Bonn, Germany

3 NeuroScience Research Center, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany

4 Department of Animal Ecology, Evolution and Biodiversity, Ruhr-University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany

5 author to whom correspondence should be addressed, Eva M. Neuhaus, NeuroScience Research Center, Charité, Charitéplatz 1, 10117 Berlin, Germany

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BMC Evolutionary Biology 2011, 11:234  doi:10.1186/1471-2148-11-234

Published: 9 August 2011

Abstract

Background

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. 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.

Results

We 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.

Conclusions

GPRC5 receptors, a class of G protein-coupled receptors with unique sequence characteristics, may represent a molecular novelty that helped non-chordates to become chordates.

Keywords:
GPRC5; chordate development; retinoic acid; phylogeny; GPCR