GENE STRUCTURE AND SEQUENCE

基因结构和序列

• 批准号: 3293952
• 负责人: WALTER GILBERT
• 金额: $ 52.01万
• 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/3293952
• 关键词: Agnatha; Aspergillus; Aves; Chondrichthyes; Chordata; Drosophilidae; Fungi; Malacostraca; Methanobacteriaceae; algae; angiosperms; animal population genetics; biochemical evolution; biotechnology; chickens; computer data analysis; computer graphics /printing; corn; eukaryote; genes; genetic library; genetic manipulation; genetic mapping; genetic recombination; glycolysis; laboratory rabbit; molecular cloning; nucleic acid probes; nucleic acid sequence; nucleic acid structure; plant population genetics; plants; plasmids; protein folding; protein sequence; 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 检验原始基因是由外显子拼凑而成的假设 因此蛋白质结构是在三个维度上建立起来的 对应于外显子产物的“模块”，然后可能折叠 准独立。 古代基因是那些用于基本生化的基因 在分裂成原核生物之前完全进化的过程 真核生物。 糖酵解酶磷酸丙糖异构酶的基因 (TIM) 和丙酮酸激酶 (PK) 将从多种克隆中克隆 生物：古细菌、真菌、古代和现代植物以及 动物以推断其内含子/外显子的清晰进化树 模式。 目标是对课程有一个清晰的了解 真核生物发展过程中基因结构的进化 过去十亿年半的时间，并推断基因是如何在 三十亿年前，进化的最初阶段。 这 证明基因是由“迷你基因”组合而成，因此 最初由“迷你蛋白质”组合而成的蛋白质都会发生变化 一个人对进化过程和难易程度的看法并重申 蛋白质折叠问题以更容易解决的形式。 为了支持这项工作，需要更快速的 DNA 测序技术 将被开发。 最初的目标是提高 单个工人的序列测定水平为每周 10kb。 这 下一个目标是达到每周 50kb 的水平。 这涉及到 将测序速率提高一到两个数量级 目前的技术。 这将通过应用基因组学来完成 测序技术用于分析克隆的真核序列 粘粒并直接连接至细菌序列。 长期目标是使 可以在一周内对粘粒进行测序，从而提高 序列获取达到两个兆碱基/人年的水平，以便 一个人就可以对整个细菌进行测序。 这样的增加 速率将深刻改变我们对基因序列的认识，并使之成为可能 可以对人类基因组的相当一部分进行测序。