COMPREHENSIVE COMPUTER ANALYSIS OF E COLI GENES

预计在2-3年内，几个完整的序列 细菌基因组将可用。一种适合计算机的策略 对这些基因组的分析对于成功开发 比较细菌基因组学。考虑到这一进展，我们 对现有的编码蛋白质序列进行了详细的分析 在大肠杆菌的染色体上，可以说是研究最好的 细菌。这项工作同时也是未来基因组的一个试点项目。 对新功能预测的研究和系统努力 细菌蛋白质及其真核同源物。一台详细的计算机 2328个蛋白质序列的分析，约占大肠杆菌总数的60% 使用数据库筛选的方法进行基因产品 单独的序列和比对块。令人惊讶的高比例 约86%的大肠杆菌蛋白显示出显著的序列相似性 与当前数据库中的其他蛋白质相比较；约70%的蛋白质在 至少在远亲细菌的水平上，大约40%含有 在真核或古生物蛋白质中保守的区域。对于90%以上的 大肠杆菌蛋白质，无论是功能信息还是重要的 序列相似性，或两者兼而有之。约46%的大肠杆菌 蛋白质属于286个种内同源物(Paralog)簇 被定义为具有显著的成对相似性。另外10%可能是 包括在使用敏感方法检测保守基序的簇中。 大多数集群只包括两到四个成员。在……里面 相比之下，近25%的大肠杆菌蛋白质属于四大类 并列动物的类别。这些类别包括Perimes、ATPase和 具有保守的“Walker-type”基序的GTP酶；螺旋-转弯-螺旋 调节蛋白；以及二核苷酸结合蛋白。编码基因 类似的蛋白质非随机分布在染色体上。 与大肠杆菌蛋白质的序列相似性使我们能够预测 一些重要的真核基因的可能功能，包括 其中几家公司的产品与人类疾病有关。我们得出结论 细菌蛋白质序列通常高度保守 进化，并使用当前可用的数据库和方法 他们的筛选，详细的计算机分析产生了关于 细菌基因组中绝大多数基因的功能。这个 该项目的意义在于制定了一项 基因组水平上的蛋白质序列比较分析。

It is expected that within 2-3 years several complete sequences of bacterial genomes will be available. An adequate strategy for computer analysis of these genomes is essential for the successful development of comparative bacterial genomics. In anticipation of this progress, we undertook a detailed analysis of the available protein sequences encoded in the chromosome of Escherichia coli, arguably the best studied bacterium. This work is simultaneously a pilot project for future genome studies and a systematic effort on prediction of new functions of bacterial proteins and their eukaryotic homologs. A detailed computer analysis of 2,328 protein sequences comprising about 60% of the E. coli gene products was performed using methods for database screening with individual sequences and alignment blocks. A surprisingly high fraction of E. coli proteins - about 86% - showed significant sequence similarity to other proteins in current databases; about 70% show conservation at least at the level of distantly related bacteria, and about 40% contain regions conserved in eukaryotic or Archaeal proteins. For over 90% of the E. coli proteins, either functional information, or significant sequence similarity, or both, are available. About 46% of the E. coli proteins belong to 286 clusters of intraspecies homologs (paralogs) defined as having significant pairwise similarity. Another 10% could be included in clusters using sensitive methods to detect conserved motifs. The majority of the clusters include only two to four members. In contrast, nearly 25% of all E. coli proteins belong to the four largest classes of paralogs. These classes include permeases; ATPases and GTPases with the conserved "Walker-type" motif; helix- turn-helix regulatory proteins; and dinucleotide-binding proteins. Genes encoding paralogous proteins are non-randomly distributed along the chromosome. Sequence similarity with E. coli proteins allowed the prediction of possible functions of a number of important eukaryotic genes, including several whose products are implicated in human diseases. We conclude that bacterial protein sequences generally are highly conserved in evolution, and with the currently available databases and methods of their screening, detailed computer analysis yields information on the functions of the vast majority of genes in a bacterial genome. The significance of the project is in the development of a strategy for comparative analysis of protein sequences at a genome scale.