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: 6526065
• 负责人: LAURA F LANDWEBER
• 金额: $ 18.79万
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6526065
• 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：这是一个研究的机制和演变的建议， 黏菌线粒体基因中广泛的RNA编辑， DNA重排发生在纤毛虫体细胞大核 由生殖细胞微核形成。 数学模型， 描述了RNA编辑和DNA重排过程， 还将对生物体进行调查。 本研究项目由三部分组成。 第一部分是关于 随着线粒体RNA编辑进化的重建， 黏菌的基因和纤毛虫的DNA重排系统， 系统发育方法 为此，PI 打算建造一个 不同种类黏菌的可靠系统发育树， 纤毛虫使用核糖体RNA序列，然后推断进化的四个 不同类型的RNA编辑和各种类型的DNA重排， 黏菌和纤毛虫的历史使用简约法。 大卫医生 普雷斯科特同意在这个项目上合作。 研究的第二部分是一个实验研究，以了解 棘尾虫DNA重排的分子机制 现在 已知一些生殖系基因由插入的非编码DNA组成， 序列（内部消除序列; IES）和大核目的基因 序列（MDS）和大核形成过程中的 IES被消除，MDS以奇怪的顺序组合形成 功能基因 然而，不知道MDS如何按照顺序重新排列， 这与MDS在生殖系基因中的原始顺序不同。 的 P.I.计划通过一系列的实验来研究DNA重排的机制， 涉及DNA转化、遗传分析和PCR的功能性实验 分析重新安排的时间进程，以测试 不同的重组模式。 这部分工作将在 Hans Lipps博士在德国的实验室。 研究项目的第三部分涉及数学 RNA编辑和DNA重排的建模。 据说DNA 重排过程类似于有向哈密顿路径问题， 数学和重排是数学上非常有效的。 的 P.I. 现在我想发展一个更好的数学理论来描述这个 过程 这部分工作将与L. Kari（西安大略大学）和G. 罗森贝格（莱顿 大学）。