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 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.

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…Using this approach, it was found that the URP1 and URP2 genes, although present only in fish, emerged long before the tetrapod/fish split and thus represent two distinct paralogous genes, in addition to the UII and URP genes. As mentioned in section II.C, a true ortholog of the URP gene does also exist in teleosts and was recently characterized (Quan et al, 2012;Tostivint et al, 2014). As in tetrapods, teleost URPs possess a single residue extension at their C terminus.…”

“…In tetrapods, the coding sequence of URP is located in the fifth exon , whereas, in teleosts, it is split between exons 4 and 5 (Quan et al, 2012). As mentioned above (see section II.J), two additional paralogous genes of the UII family have been characterized in actinopterygians and sarcopterygians and have been called URP1 and URP2 (Nobata et al, 2011;Tostivint et al, 2013Tostivint et al, , 2014. In zebrafish, both URP1 and URP2 genes contain five exons and, for each gene, the coding sequence of the mature peptide is located on the last exon (Parmentier et al, 2011).…”

Molecular characterization and expression of three preprosomatostatin genes and their association with growth in common carp (Cyprinus carpio)

“…Somatostatin has been of interest to researchers due to not only its important function on the regulation of growth (Melmed et al, 1996), but also the complex evolution history of its family genes in vertebrates (Tostivint et al, 2008(Tostivint et al, , 2014. The latest round of whole-genome duplication which has been estimated to have occurred approximately 8.2 million years ago has caused extensive gene duplications in C. carpio (Xu et al, 2014).…”

“…Recently, two other SS variants, somatostatin 5 (SS5) and somatostatin 6 (SS6) were isolated from zebrafish (Danio rerio) (Liu et al, 2010), then subsequently found in several other fish species Tostivint et al, 2013Tostivint et al, , 2014. All of these mature somatostatins are located at the C-terminal of their precursor proteins (preprosomatostatin, PSS), which are encoded by preprosomatostatin genes (Tostivint et al, 2008).…”

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

“…Somatostatin and urotensin II are two cyclic neuropeptides that have recently been shown to derive from a single ancestral gene (Tostivint et al 2006). In this review, the authors discuss the evolutionary dynamics of somatostatin/urotensin II peptides and their receptors that have led to the unexpected complexity of these neuroendocrine systems (Tostivint et al 2014). The identification of growth hormone secretagogue receptor (GHSR) and its natural ligand ghrelin is a striking example of the power of target base drug discovery, also termed 'reverse pharmacology', for the development of innovative therapeutic compounds (Kojima & Kangawa 2010).…”