Somatostatin and its receptors from fish to mammals

Somatostatin (SST) and its receptors (sst) make up a molecular family with unique functional complexity and versatility. Widespread distribution and frequent coexpression of sst subtypes underlies the multiplicity of (patho)physiological processes controlled by SST (central nervous system functions, endocrine and exocrine secretion, cell proliferation). This complexity is clearly reflected in the intricate evolutionary development of this molecular family. Recent studies postulate the existence of an ancestral somatostatin/urotensin 11 (SST/UII) gene, which originated two ancestral, SST and UII, genes by local duplication. Subsequently, segment duplication would have originated two diverging SST genes in both fish (SS1/SS2) and tetrapods [(SST/cortistatin(CST))]. SST/CST actions are mediated by a family of GPCRs (sst1-5) encoded by five different genes. sst1-4 sequences are highly conserved compared with sst5, suggesting unique evolutionary and functional relevance for the latter. Indeed, we recently identified novel truncated but functional sst5 variants in several species, which may help to explain part of the complexity of the SST/CST/sst family. Comparative and phylogenetic analysis of this molecular family would enhance our understanding of its paradigmatic evolutionary complexity and functional versatility.