Analysis of a Novel Mechanism of Genetic Reversion in Arabidopsis

拟南芥遗传逆转新机制的分析

• 批准号: 0321978
• 负责人: Robert Pruitt
• 金额: --
• 依托单位: Purdue University
• 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: 2003-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0321978&HistoricalAwards=false
• 关键词: Analysis; Novel; Mechanism; Genetic; Reversion

The stability and integrity of the genetic material, deoxyribonucleic acid (DNA), is dependent upon a myriad of cellular processes. Since most organisms continue to experience cell division after achieving maturity, replication and repair of the genome remain essential for normal growth and development throughout the life span of that organism. A host of universal and relatively well-understood DNA repair systems exist to ensure genomic integrity. In recent years, ribonucleic acid (RNA) has been demonstrated to play important roles far beyond those of messenger RNA, transfer RNA and ribosomal RNA. RNA has been shown to play a catalytic role in various RNAse enzymes and most recently has been shown to play a role in regulating gene expression by targeting specific messenger RNAs for degradation. The research to be carried out will characterize a novel mechanism of genetic reversion that may represent a case of template-directed DNA modification where the template directing the modification is RNA. Specifically, this project aims to understand the nature of the genetic instability seen in a collection of mutants in the model plant, Arabidopsis thaliana, that have genetic lesions in the HOTHEAD gene. Although the HOTHEAD gene product itself shares only superficial homology with a class of enzymes involved in degradation of cyanogenic compounds and does not feature any motifs typical of DNA-associated proteins, this gene appears to be susceptible to a novel type of genetic reversion. Single point mutations in hothead alleles revert to the wild-type nucleotide sequence at a high frequency. Furthermore, genotypically wild-type plants derived from heterozygous hothead parent plants show a similar instability, but in this case involving alteration back to the mutant allele in what appears to be an allele-specific manner. The instability of the genetic material seen in the HOTHEAD gene may represent a general mechanism that allows the organism to maintain additional DNA sequence variation beyond the two alleles of each gene present in the chromosomes.

遗传物质脱氧核糖核酸(DNA)的稳定性和完整性取决于无数的细胞过程。由于大多数生物在达到成熟后继续经历细胞分裂，因此基因组的复制和修复对于该生物整个生命周期的正常生长和发育仍然是必不可少的。存在许多普遍且相对为人所知的DNA修复系统，以确保基因组的完整性。近年来，核糖核酸(RNA)被证明发挥着远远超过信使RNA、转移RNA和核糖体RNA的重要作用。RNA已被证明在各种RNase酶中起催化作用，最近被证明通过靶向特定的信使RNA降解而在调节基因表达方面发挥作用。即将开展的研究将表征一种新的遗传逆转机制，该机制可能代表模板导向的DNA修饰的情况，其中指导修饰的模板是RNA。具体地说，这个项目旨在了解在模式植物拟南芥中的一系列突变体中发现的遗传不稳定性的性质，这些突变体在辣头基因中存在遗传损伤。尽管辣头基因产物本身与一类参与降解含氰化合物的酶只有表面上的同源性，并且没有任何典型的DNA相关蛋白质基序，但该基因似乎容易发生一种新型的遗传逆转。冲动等位基因的单点突变以较高的频率恢复为野生型核苷酸序列。此外，从杂合的冲动亲本植物衍生的野生型植株也表现出类似的不稳定性，但在这种情况下，涉及到以一种似乎是等位基因特有的方式转换回突变的等位基因。辣头基因中遗传物质的不稳定性可能代表了一种普遍的机制，即允许有机体保持额外的DNA序列变异，而不是存在于染色体中的每个基因的两个等位基因。