UNDERSTANDING COMPLEX GENE EDITING SYSTEMS IN PROTISTS

了解原生生物的复杂基因编辑系统

• 批准号: 6182038
• 负责人: LAURA F LANDWEBER
• 金额: $ 17.73万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6182038
• 关键词: Myxomycophyta; Protista; biochemical evolution; biological information processing; gene rearrangement; genetic mapping; genetic markers; mathematical model; mitochondria; model design /development; polymerase chain reaction; posttranscriptional RNA processing

DESCRIPTION: This is a proposal to study the mechanism and evolution of the extensive RNA editing in mitochondrial genes in slime molds and the intriguing DNA rearrangement that occurs in ciliates when the somatic macronucleus is formed from the germline micronucleus. Mathematical models that would describe the RNA editing and the DNA rearrangement processes in these organisms will also be investigated. This research project consists of three parts. The first part is concerned with the reconstruction of the evolution of the RNA editing of mitochondrial genes in slime molds and the DNA rearrangement systems in ciliates using a phylogenetic approach. For this purpose, the P.I. intends to construct a reliable phylogenetic tree for different groups of species of slime molds and ciliates using ribosomal RNA sequences and then infer the evolution of four different types of RNA editing and various types of DNA rearrangements in the history of slime molds and ciliates using the parsimony method. Dr. David Prescott has agreed to collaborate in this project. The second part of the research is an experimental study to understand the molecular mechanisms of DNA rearrangement in Stylonychia lemnae. It is now known that some germline genes are composed of intervening non-coding DNA sequences (internally eliminated sequences; IESs) and macronuclear destined sequences (MDSs) and that in the process of formation of the macronucleus IES's are eliminated and MDSs are combined in a strange order to form functional genes. However, it is unknown how MDSs are rearranged in the order which is different from the original order of MDSs in the germline gene. The P.I. plans to study the mechanisms of DNA rearrangement through a series of functional experiments involving DNA transformation, genetic analysis, and PCR analysis of the time-course of rearrangement to test specific aspects of different models of rearrangements. This part of the work will be done in the laboratory of Dr. Hans Lipps in Germany. The third part of the research project is concerned with the mathematical modeling of RNA editing and DNA rearrangement. It is stated that the DNA rearrangement process is similar to a directed Hamiltonian path problem in mathematics and that the rearrangement is mathematically very efficient. The P.I. now wants to develop a better mathematical theory for describing this process. This part of the work will be done in collaboration with Dr. L. Kari (University of Western Ontario) and Dr. G. Rozenberg (Leiden University).

描述：这是研究研究机制和演变的建议 粘液模具中线粒体基因中的大量RNA编辑和吸引人的 当体细胞核中的纤毛中发生的DNA重排 由种系微核形成。 数学模型 描述其中的RNA编辑和DNA重排过程 也将研究生物。 该研究项目由三个部分组成。 第一部分 通过重建线粒体的RNA编辑的演变 粘液模具中的基因和纤毛中的DNA重排系统使用A 系统发育方法。 为此，P.I. 打算构建一个 可靠的系统发育树，用于不同种类的粘液霉菌和 使用核糖体RNA序列纤毛，然后推断出四个 不同类型的RNA编辑和各种类型的DNA重排 使用简约方法的粘液模具和纤毛的历史。 大卫博士 普雷斯科特（Prescott）已同意在该项目中进行合作。 研究的第二部分是一项实验研究，以了解 Stylonychia Lemnae中DNA重排的分子机制。 现在 知道某些种系基因由中间的非编码DNA组成 序列（内部消除序列； IESS）和大核注定 序列（MDS），并且在大核形成过程中 IES被消除，MDS以一个奇怪的顺序组合形成 功能基因。 但是，尚不清楚如何按顺序重新安排MDS 这与种系基因中MDS的原始顺序不同。 这 P.I.计划通过一系列研究DNA重排的机制 涉及DNA转化，遗传分析和PCR的功能实验 分析重排的时间顺序测试的特定方面 不同的重排模型。 这部分工作将在 德国汉斯·利普斯（Hans Lipps）博士实验室。 研究项目的第三部分与数学有关 RNA编辑和DNA重排的建模。 据说DNA 重排过程类似于指向的哈密顿路径问题 数学和重排在数学上非常有效。 这 P.I. 现在想发展一个更好的数学理论来描述这一点 过程。 这部分工作将与L博士合作完成。 卡里（西安大略大学）和G. Rozenberg博士（莱顿 大学）。