Molecular divergence of the fish somatomedins: the single family of insulin­like growth factor (IGF)-I and -II from the teleost, flounder

The teleosts represent ancient real-bony vertebrates in phylogeny and resemble major genetic patterns to higher vertebrates. In the present study, we have defined the single family of insulin-like growth factors (IGFs) from flounder (Paralichthys olivaceus), compared to the prototype of IGFs observed in the Agnathan hagfish. In flounder, IGFs are clearly diverged into two major types including type I and II, and they are structurally similar by displaying a multidomain structure consisting of five functional regions as previously found in other vertebrates. However, flIGF-I appears to be more basic (pI 8.03) than the flIGF-II (pI 5.34) in the fully processed form for the B to D domain region. The flIGF-I seems to contain an evolutionary conserved Asn-linked glycosylation in E domain, which is not found in flIGF­II. The most interesting feature is that flIGF-II appeared to be structurally close to hagfish IGF in secondary structures, particularly in Band D domains. This could tell us an idea on the molecular divergence of IGFs from the Agnatha to teleosts during the vertebrate phylogeny. It also support, in part, a notion regarding on how IGF-II is appeared as more embryonic during development. Nonetheless, the biologically active B to D domain region of flIGF-II shows significant sequence homology of $65.6\%$ to flIGF-Is and contains the evolutionary conserved insulin-family signature, as well as a reserved recognition site (Lys) in D domain, necessary to generate proteolytic cleavage for E-peptide. A significant structural difference was found in E domain in which flIGF-I possesses two potential alternative splicing donor site at $Val^{17,\;24}$ of E domain. Therefore, it seems so far that IGF-I sorely produces spliced variants due to the spliced E-peptide moiety while IGF-II appears to be maintained in a single type during evolution. IGF-II, however, may be also possible to transcribe unidentified variants, depending on the physiological conditions of tissues in vertebrates in vivo.