MOLECULAR EVOLUTION OF GPCRS: What we know and what the future holds

    1. Hubert Vaudry
    1. INSERM U982, International Associated Laboratory Samuel de Champlain, PRIMACEN, IRIB, University of Rouen, 76821 Mont-Saint-Aignan, France
    1. Correspondence should be addressed to H Vaudry; Email: hubert.vaudry{at}

    G protein-coupled receptors (GPCRs) are the largest family of cell membrane receptors in the human genome, comprising ∼2% of human proteins. GPCRs are the target of a variety of signaling molecules such as peptide hormones, neuropeptides, chemokines, neurotransmitters, nucleotides, steroids, prostaglandins, cannabinoids, odorants, taste molecules, pheromones, and ions. A large number of clinically used drugs exert their biological effects via a GPCR, and orphan GPCRs provide valuable targets for the discovery of innovative drugs. Thus, it did not come as a surprise that the 2012 Nobel Prize in Chemistry was awarded to Robert J Lefkowitz and Brian K Kobila for their pioneer work on GPCR structures and functions.

    The presence of GPCRs in the genome of all living organisms including bacteria, yeast, plants, invertebrates, and vertebrates shows the early evolutionary origin of these ubiquitous and versatile receptors. As a result of two major whole-genome duplication rounds during vertebrate evolution (Van de Peer et al. 2010), GPCRs have had the opportunity to explore new functions (neofunctionalization) while maintaining the ancient ones. In particular, in the case of …

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