Physiological and Molecular Causes of Genetic Variation/Covariation Inendocrine Regulation

遗传变异/共变异内分泌调节的生理和分子原因

• 批准号: 0212486
• 负责人: Anthony Zera
• 金额: --
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0212486&HistoricalAwards=false
• 关键词: Physiological; Molecular; Causes; Genetic; Variation

Although a tremendous amount of information is available on physiological, biochemical, and molecular aspects of endocrinology, very little is known about the evolution of endocrine regulation. Genetically-based variations in endocrine traits provide the raw material upon which natural selection acts during the initial stages of adaptive evolution. Thus, a key step in understanding the evolution of hormonal control is the characterization of genetically-based variation in endocrine regulators within species. The goal of the present multi-disciplinary study is to identify the variable molecular and physiological factors that cause genetically-based variation in the enzyme juvenile hormone esterase (JHE) in a cricket species. JHE degrades and regulates the key insect hormone, juvenile hormone, and has been the subject of intensive study in the Principal Investigator's laboratory during the past 15 years. This proposal has three primary research objectives. First, using both in vivo and in vitro approaches, the following hypothesis will be tested: genetic variation in the concentration of or tissue sensitivity to neurohormones causes genetically based variation in JHE activity and tissue distribution. Experiments will largely involve assessing the effect of extracts or implants of neural tissue derived from high- or low- JHE activity genetic stocks on JHE activity and related endocrine traits in the same vs alternate lines. Second, the role of variation in JHE messenger RNA abundance as the cause of genetically-based variation in JHE activity will be tested. JHE mRNA abundance will be compared between high and low activity lines using Northern blots employing a probe derived from a recently obtained, nearly full-length JHE cDNA. Third, the high and low JHE activity lines will be crossed and backcrossed to determine the degree of co-segregation among (1) JHE activity and associated endocrine traits, (2) molecular correlates of these traits (JHE mRNA level), and (3) potential regulators of these traits. This research will simultaneously provide important new information for several different areas of biology. This will be the first study to identify the molecular and physiological causes of genetically-based variation in an endocrine regulator in natural populations. This project will result in the first detailed synthesis of endocrine physiology, molecular biology, and quantitative genetics. Finally, these studies will constitute the first investigations of genetic variation in neuroendocrine regulation in natural populations and will set the stage for subsequent identification of these regulators and the genes that encode them.

尽管关于内分泌学的生理、生化和分子方面有大量信息，但人们对内分泌调节的演变知之甚少。 内分泌性状的遗传变异为适应性进化的初始阶段的自然选择提供了原材料。 因此，了解激素控制进化的关键一步是表征物种内内分泌调节因子的遗传变异。目前多学科研究的目标是确定导致蟋蟀物种中保幼激素酯酶（JHE）发生遗传变异的可变分子和生理因素。 JHE 降解和调节关键的昆虫激素——保幼激素，在过去 15 年里一直是首席研究员实验室深入研究的课题。 该提案有三个主要研究目标。 首先，使用体内和体外方法，将测试以下假设：神经激素浓度或组织敏感性的遗传变异导致 JHE 活性和组织分布的遗传变异。 实验主要涉及评估来自高或低 JHE 活性遗传储备的神经组织提取物或植入物对相同品系与备用品系中 JHE 活性和相关内分泌性状的影响。其次，将测试 JHE 信使 RNA 丰度变异作为 JHE 活性遗传变异原因的作用。 将使用 Northern 印迹法比较高活性系和低活性系之间的 JHE mRNA 丰度，该探针采用源自最近获得的几乎全长 JHE cDNA 的探针。 第三，将高和低 JHE 活性品系进行杂交和回交，以确定 (1) JHE 活性和相关内分泌性状、(2) 这些性状的分子相关性（JHE mRNA 水平）和 (3) 这些性状的潜在调节因子之间的共分离程度。这项研究将同时为生物学的几个不同领域提供重要的新信息。这将是第一项确定自然群体中内分泌调节剂遗传变异的分子和生理原因的研究。 该项目将首次对内分泌生理学、分子生物学和定量遗传学进行详细综合。最后，这些研究将构成对自然群体中神经内分泌调节遗传变异的首次研究，并将为随后识别这些调节因子和编码它们的基因奠定基础。