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

硬骨鱼胰岛素超家族的进化：多样化、亚功能化和广盐适应中的作用

• 批准号: RGPIN-2014-06203
• 负责人: Good, Sara
• 金额: $ 1.75万
• 依托单位: University of Winnipeg
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=588866
• 关键词: Evolution; insulin; superfamily; teleosts; diversification

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.

在我们对脊椎动物基因组进化的理解及其对现代脊椎动物中出现的各种基因家族的深刻影响方面，已经取得了惊人的进展。这些发现之一是脊椎动物基因家族的多样化受到全基因组复制（WGD）事件的强烈影响，其中之一发生在鳍鱼进化的早期。在这些WGD事件中，某些类型的基因被优先保留，例如跨膜受体和其他信号分子;人们认为，参与信号通路的基因网络的复制为对环境线索的复杂生理和神经反应的发展提供了机会，这是脊椎动物生物体的标志。在我的研究项目中，我们正在研究驱动胰岛素超家族受体信号系统的2个亚类多样化的进化和功能机制：1）松弛素样肽（包括RLN和胰岛素样肽，INSL）和2）胰岛素（INS）和胰岛素样生长因子（IGF），以及它们在非哺乳类脊椎动物（主要是硬骨鱼）中的同源受体。在以前的工作中，我们表明，所有的胰岛素超家族的配体和受体的WGD事件大大多样化，而且，鱼保留了大量的基因，来自鱼的特异性WGD。此外，我们发现，鱼大大放大了受体的数量相比，配体（激素）基因，这表明配体-受体对可能会采取新的或专门的功能，因为受体不同的时间（阶段）或空间（组织）的表达或在他们引起的信号反应。在这个建议中，我们概述了胰岛素超家族的三个主要研究项目。在第一个项目中，我们专注于精确定位特定的配体-受体配对和功能多样化的一个不同的亚组的Rln/Insl肽puppuridine参与神经内分泌调节。在第二个项目中，我们提出了一个完整的进化分析的INS/IGF及其受体的硬骨鱼。令人惊讶的是，尽管INS/IGF基因在哺乳动物中已经得到了很好的研究，由于其在健康科学中的应用，但在硬骨鱼类中INS/IGF和受体基因的进化关系，起源和多样性还没有得到很好的理解，这限制了功能研究。理解这个进化框架是完成我们的第三个项目的基础，在该项目中，我们建议在非哺乳动物物种中进行胰岛素超家族基因的第一次群体水平分析，以测试有关胰岛素超家族基因在淡水（FW）适应棘鱼过程中的选择作用的假设。胰岛素超家族的几个成员被假设在盐水（SW）FW适应中发挥直接作用，因为他们假设的作用，而其他成员的家庭可能会影响SW/FW适应间接通过生理变化，发生在SW与FW环境中的生长和繁殖。总的来说，这些项目将贡献有关硬骨鱼类基因组进化和调控的基础知识，特别是在物种和种群水平上配体-受体系统亚功能化的过程，这是我们实验室的长期研究主题。其次，项目2和3还将提供有关硬骨鱼类胰岛素超家族基因的进化和功能的基本知识，特别是它们在SW和FW之间的适应中的作用，这一过程对所有溯河产卵或广盐性硬骨鱼物种都是相关和重要的，包括加拿大的几个经济上重要的渔业物种。