GENE STRUCTURE AND SEQUENCE

将分析古老基因的内含子/外显子结构， 检验原始基因是由外显子拼凑而成的假设 因此蛋白质的结构是由 对应于外显子产物的“模块”，然后可以折叠 准独立。 古代基因是那些基本的生化 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基因 (TIM)和丙酮酸激酶（PK）将从各种各样的 生物：古细菌，真菌，古代和现代植物， 为了推导出一个清晰的内含子/外显子的进化树， 模式. 目的是要清楚地了解 基因结构的进化在真核生物的发展过程中， 过去十亿半年，并推断基因是如何组装在一起的。 30亿年前进化的最开始 的 证明基因是由“迷你基因”组合而成的，因此， 蛋白质最初是从“迷你蛋白质”组合在一起的， 一个人对进化过程和容易程度的看法，并重申 蛋白质折叠问题的一种更容易解决的形式。 为了支持这项工作，更快速的DNA测序技术 将被开发。 最初的目标将是提高 对于单个工人，将序列测定提高到10 kb/周的水平。 的 下一个目标是达到每周50 kb的水平。 这涉及 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 测序技术分析克隆的真核生物序列， 直接用于细菌序列。 长期目标是使 在一周内完成一个粘粒的测序是可能的，因此， 序列采集达到2兆/人-年的水平，因此， 一个人就能测序整个细菌 的这种增加 会深刻地改变我们对基因序列的认识， 可以对人类基因组的可观部分进行测序。

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.