Evolution of the insulin superfamily in teleosts: diversification, sub-functionalization and role in euryhaline adaptation

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There has been phenomenal progress in our understanding of vertebrate genome evolution and its profound impact on the emergence of diverse arrays of gene families in modern day vertebrates. One of these findings is that the diversification of vertebrate gene families has been strongly influenced by whole genome duplication (WGD) events, one of which occurred early in ray-finned fish evolution. Some classes of genes were preferentially retained during these WGD events, such as transmembrane receptors and other signalling molecules; it is thought that duplication of gene networks involved in signalling pathways opened up opportunities for the development of complex physiological and neurological responses to environmental cues, a hallmark of vertebrate organisms. In my research program, we are investigating the evolutionary and functional mechanisms driving the diversification of 2 sub-classes of insulin superfamily hormone-receptor signalling systems: 1) relaxin-like peptides (including RLN and insulin like peptides, INSL) and 2) insulin (INS) and insulin-like growth factors (IGF), and their cognate receptors in non-mammalian vertebrates, primarily teleosts. In previous work we showed that all of the ligands and receptors in the insulin superfamily were greatly diversified by WGD events and furthermore that fish retained a large number of the genes derived from the fish-specific WGD. Additionally, we uncovered that fish have greatly amplified the number of receptor compared to ligand (hormone) genes suggesting that ligand-receptor pairs may adopt new or specialized functions because receptors differ in their temporal (stage) or spatial (tissue) expression or in the signalling responses they elicit. In this proposal, we outline three major research projects on the insulin superfamily. In the first project, we focus on pinpointing the specific ligand-receptor pairings and functional diversification of a diverse subgroup of Rln/Insl peptides putatively involved in neuroendocrine regulation. In the second project, we propose a full evolutionary analyses of INS/IGF and their receptors in teleosts. Surprisingly, although INS/IGF genes have been well studied in mammals due to their application in health sciences, the evolutionary relationship, origin and diversity of INS/IGF and receptor genes in teleosts is not well understood, which limits functional studies. Understanding this evolutionary framework is fundamental to completing our third project, in which we propose to perform the first population-level analyses of insulin superfamily genes in a non-mammalian species to test hypotheses about the role of selection on insulin superfamily genes during fresh-water (FW) adaptation in stickleback. Several members of the insulin superfamily are hypothesized to play direct roles in salt water (SW) to FW adaptation because of their hypothesized roles in osmoregulation while other members of the family may influence SW/FW adaptation indirectly via physiological changes that occur in growth and reproduction in SW vs FW environments. Collectively, these projects will contribute fundamental knowledge regarding genome evolution and regulation in teleosts, particularly the process of sub-functionalization of ligand-receptor systems at the levels of species and populations, long-term research themes in our laboratory. Secondly, projects 2 and 3 will also provide fundamental knowledge regarding the evolution and function of insulin superfamily genes in teleosts, in particular their role in adaptation between SW and FW, a process that is relevant and important for all anadromous or euryhaline teleost species, including several economically important fisheries species for Canada.