GENE STRUCTURE AND SEQUENCE

基因结构和序列

• 批准号: 3293949
• 负责人: WALTER GILBERT
• 金额: $ 65.09万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-03-01 至 1992-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3293949
• 关键词: Aspergillus; Fungi; Methanobacteriaceae; algae; angiosperms; animal population genetics; biochemical evolution; biotechnology; computer data analysis; computer graphics /printing; corn; eukaryote; genes; genetic library; genetic manipulation; genetic mapping; genetic recombination; glycolysis; molecular cloning; nucleic acid sequence; nucleic acid structure; plant population genetics; plants; plasmids; pyruvate kinase; radiotracer; triose phosphate isomerase

The intron/exon structure of ancient genes will be analysed in order to test the hypothesis that the original genes were pieced together from exons and thus that protein structures are built up in three dimensions from 'modules' that correspond to the exon products, which may then fold quasi-independently. Ancient genes are those for basic biochemical processes that evolved fully before the split into prokaryotes and eukaryotes. The genes for the glycolytic enzymes triosephosphate isomerase (TIM) and pyruvate kinase (PK) will be cloned from a wide variety of organisms: archaebacteria, fungi, and ancient and modern plants and animals in order to deduce a clear evolutionary tree of their intron/exon patterns. The goal is to develop a clear understanding of the course of evolution of gene structure over the development of the eukaryotes, the last billion and a half years, and to infer how the genes were assembled at the very beginning of evolution, three billion years ago. The demonstration that genes were put together from 'mini-genes' and hence that proteins were first put together from 'mini-proteins' will both change one's conception about the course and ease of evolution and restate the protein folding problem in a form easier of solution. To support this work, techniques for the still more rapid sequencing of DNA will be developed. The initial goal will be to increase the rate of sequence determination to a level of 10kb/week for a single worker. The next target will be to achieve a level of 50kb/week. This involves increasing the rate of sequencing by one to two orders of magnitude over the current technology. This will be done by applying the genomic sequencing techniques to the analysis of eukaryotic sequences cloned in cosmids and to bacterial sequences directly. The long term goal is to make it possible to sequence a cosmid in a week, and thus to bring the rate of sequence aquisition to the level of two megabases/person-year, so that single individual can sequence an entire bacterium. Such an increase in rate would profoundly change our knowledge of gene sequence and make it possible to sequence appreciable portions of the human genome.

将分析古代基因的内含子/外显子结构，以便为了 检验原始基因从外显子拼凑在一起的假设 因此，蛋白质结构是从三个维度建立的 与外显子产品相对应的“模块”，然后可以折叠 准依赖性。 古代基因是基本生化的基因 在分解为原核生物之前完全进化的过程和 真核生物。 糖酵解酶三尿磷酸异构酶的基因 （TIM）和丙酮酸激酶（PK）将从多种 生物：考古细菌，真菌以及古代和现代植物以及 为了推断其内含子/外显子的清晰进化树 模式。 目的是要清楚地了解 基因结构在真核生物的发展中的演变， 最后十亿年半，并推断基因是如何组装的 进化的最初，三十亿年前。 这 证明基因是从“迷你生成”中汇总在一起的，因此 蛋白质首先是从“迷你蛋白质”中组装在一起的 关于课程的概念和易于进化的概念，并重申 蛋白质折叠问题的溶液更容易。 为了支持这项工作，DNA的更快测序的技术 将开发。 最初的目标是提高 单个工人的序列确定为10kb/周的水平。 这 下一个目标是达到每周50kb的水平。 这涉及 将测序率提高一到两个数量级 当前的技术。 这将通过应用基因组来完成 测序技术对克隆的真核序列进行分析 宇宙和直接进入细菌序列。 长期目标是使 可以在一周内对宇宙序列进行排序，从而带来 序列的序列至两个巨蛋/人年的水平，以便 单个人可以对整个细菌进行测序。 这样的增加 速率将深刻地改变我们对基因序列的了解，并使之成为现实 可能对人类基因组的明显部分进行序列。