Mechanisms Regulating Transcription of the Ldh-B Locus in Populations of Fundulus Heteroclitus

眼底异斜群体 Ldh-B 基因座转录调控机制

• 批准号: 9629572
• 负责人: George Somero
• 金额: $ 20.3万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-15 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9629572&HistoricalAwards=false
• 关键词: Mechanisms; Regulating; Transcription; Ldh; Locus

9629572 Powers Differences in the expression of genes that encode intracellular enzymes are a particularly important potential source of genetic diversity for species; these differences may provide the kind of genetic plasticity that allow adaptation to large changes in environmental parameters, like temperature, salinity, and others. While studies documenting changes in gene expression in relation to such environmental parameters are few, studies delineating the mechanisms responsible for these changes are even fewer. The present research project will provide one of the very few detailed studies of the molecular mechanisms that differentially regulate the expression of one of these loci. Dr. Powers and his colleagues take advantage of the well characterized model teleost, Fundulus heteroclitus, and an equally well characterized gene system, i.e., the intracellular enzyme common to heart and other aerobic red muscle tissue, the lactate dehydrogenase-B gene (Ldh-B). Because the teleost model is distributed along the east coast of North America, i.e., from Newfoundland to Florida, populations at the extremes of the species range are exposed to very different environmental temperatures. Since fish are "cold blooded" animals, this temperature difference could have a profound effect on them, if there were no compensatory adaptive changes. One such change already uncovered is a difference in gene expression of Ldh-B between fish from the cold waters of Maine and those from the warm waters of Florida. The proposed research will delineate the detailed molecular mechanisms underlying this difference in gene regulation of Ldh-B. Factors involved in the regulation of the Ldh-B gene will be identified and variation in these factors and their functional consequences will be examined using a wide variety of modern molecular techniques. Identifying the molecular mechanisms underlying the variation in transcriptional regulation between populations of this model teleost, is a first important step toward a detailed understanding of the evolution of gene regulation, in general. In addition to addressing the basic research issue of the molecular mechanisms that underlie direct evolutionary change at the regulatory level, this research will also provide important fundamental information about the regulation of a critical enzyme system in intermediate metabolism that has not been previously determined. The new knowledge uncovered about the details of Ldh-B gene regulation will provide an important scientific basis for a better understanding of the regulation of genes encoding metabolic enzymes. This knowledge can be used to provide insight about other organisms, including humans. This study will also provide gene regulation information that may eventually be useful in the genetic engineering of disease-resistant, fast growing, environmentally safe, fish for the aquaculture industry in the future.

编码细胞内酶的基因表达差异是物种遗传多样性的一个特别重要的潜在来源;这些差异可能提供了一种遗传可塑性，允许适应环境参数的巨大变化，如温度，盐度等。 虽然记录基因表达与这些环境参数相关的变化的研究很少，但描述这些变化的机制的研究就更少了。目前的研究项目将提供一个非常少的详细研究的分子机制，差异调节这些基因座之一的表达。 Powers博士和他的同事利用了特征良好的硬骨鱼模型Fundulus heteroclitus，以及一个同样特征良好的基因系统，即，心脏和其他有氧红色肌肉组织共有的细胞内酶，乳酸脱氢酶-B基因（Ldh-B）。 由于硬骨鱼模型分布在沿着北美东海岸，即，从纽芬兰到佛罗里达，处于物种分布极端的种群暴露在非常不同的环境温度下。 由于鱼类是“冷血”动物，如果没有补偿性的适应性变化，这种温差可能会对它们产生深远的影响。 已经发现的一个变化是缅因州寒冷沃茨的鱼和佛罗里达温暖沃茨的鱼之间Ldh-B基因表达的差异。 拟议的研究将描绘Ldh-B基因调控差异的详细分子机制。将识别参与Ldh-B基因调节的因素，并使用多种现代分子技术检查这些因素的变化及其功能后果。 确定该模型硬骨鱼种群之间转录调控变化的分子机制，是详细了解基因调控进化的第一个重要步骤。 除了解决基础的分子机制，在监管层面的直接进化变化的基础研究问题，这项研究还将提供重要的基础信息的中间代谢，尚未确定的关键酶系统的调节。Ldh-B基因调控细节的新发现将为更好地理解代谢酶编码基因的调控提供重要的科学依据。 这些知识可以用来提供关于其他生物体的见解，包括人类。本研究也将提供基因调控信息，最终可能是有用的抗病，快速增长，环境安全，鱼的水产养殖业在未来的基因工程。