MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Abstract

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 threeSS(SS1,SS2, andSS5) and sixSSTR(SSTR1–6) genes, on the one hand, and fourUII(UII,URP,URP1, andURP2) and fiveUTS2R(UTS2R1–5) genes, on the other hand. In the teleost lineage, all these have been preserved with the exception ofSSTR4. Moreover, several additional genes have been gained through the 3R event, such asSS4and a second copy of theUII,SSTR2,SSTR3, andSSTR5genes, and through local duplications, such asSS3. In mammals, all the genes of the SSTR family have been preserved, with the exception ofSSTR6. In contrast, for the other families, extensive gene losses occurred, as only theSS1,SS2,UII, andURPgenes and oneUTS2Rgene are still present.