MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

    1. Dan Larhammar1
    1. Evolution des Régulations Endocriniennes, UMR 7221 CNRS and Muséum National d'Histoire Naturelle, Paris, France
      1Department of Neuroscience, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
      2Inserm U982, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Institute for Research and Innovation (IRIB), Rouen University, Mont‐Saint‐Aignan, France
    1. Correspondence should be addressed to H Tostivint, I Lihrmann or D Larhammar; Emails: htostivi{at}, isabelle.lihrmann{at} or Dan.Larhammar{at}


    Somatostatin (SS) and urotensin II (UII) are members of two families of structurally related neuropeptides present in all vertebrates. They exert a large array of biological activities that are mediated by two families of G-protein-coupled receptors called SSTR and UTS2R respectively. It is proposed that the two families of peptides as well as those of their receptors probably derive from a single ancestral ligand–receptor pair. This pair had already been duplicated before the emergence of vertebrates to generate one SS peptide with two receptors and one UII peptide with one receptor. Thereafter, each family expanded in the three whole-genome duplications (1R, 2R, and 3R) that occurred during the evolution of vertebrates, whereupon some local duplications and gene losses occurred. Following the 2R event, the vertebrate ancestor is deduced to have possessed three SS (SS1, SS2, and SS5) and six SSTR (SSTR1–6) genes, on the one hand, and four UII (UII, URP, URP1, and URP2) and five UTS2R (UTS2R1–5) genes, on the other hand. In the teleost lineage, all these have been preserved with the exception of SSTR4. Moreover, several additional genes have been gained through the 3R event, such as SS4 and a second copy of the UII, SSTR2, SSTR3, and SSTR5 genes, and through local duplications, such as SS3. In mammals, all the genes of the SSTR family have been preserved, with the exception of SSTR6. In contrast, for the other families, extensive gene losses occurred, as only the SS1, SS2, UII, and URP genes and one UTS2R gene are still present.

    • Revision received 14 March 2014
    • Accepted 10 April 2014
    • Made available online as an Accepted Preprint 16 April 2014
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