GENE STRUCTURE AND SEQUENCE

我们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，蛋白质的结构是从 与外显子产物相对应的‘模块’，然后这些外显子产物可以折叠 准独立的。古代的基因是基础生化的基因 在分裂前完全进化成原核生物和 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)将从多种不同的 生物体：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。目标是对以下过程有一个清晰的理解 真核生物发育过程中基因结构的进化 在过去的10亿年半，并推断基因是如何在 进化的开始，30亿年前。这个 证明了基因是由“微基因”组合在一起的，因此 蛋白质最初是由‘迷你蛋白质’组合而成的，两者都会发生变化 一个人对进化的过程和容易的概念，并重申 蛋白质折叠问题以一种更容易的形式解决。 为了支持这项工作，更快速的DNA测序技术 将会被开发出来。最初的目标将是提高 对于单个工人，序列测定的水平为10kb/周。这个 下一个目标将是达到50kb/周的水平。这涉及到 将测序速度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 测序技术在真核细胞序列分析中的应用 宇宙体和细菌序列的直接。长期目标是让 有可能在一周内对粘粒进行测序，从而带来 序列采集到2兆基数/人-年的水平，以便 单个个体可以对整个细菌进行测序。这样的增长 速率将深刻地改变我们对基因序列的认识，并使其 有可能对人类基因组中可察觉的部分进行测序。

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.