COMPREHENSIVE COMPUTER ANALYSIS OF E COLI GENES

预计在2-3年内， 细菌的基因组就可以得到。 计算机的适当策略 这些基因组的分析对于成功开发 比较细菌基因组学 为了取得这一进展，我们 进行了详细的分析， 在大肠杆菌的染色体中，可以说是研究得最好的 细菌。 这项工作同时也是未来基因组的试点项目 研究和系统的努力，预测新的功能， 细菌蛋白及其真核同源物。 详细的计算机 分析了2，328个蛋白质序列，包括约60%的E.杆菌 基因产物使用数据库筛选方法进行， 单独的序列和比对块。 一个令人惊讶的高比例 大肠大肠杆菌蛋白-约86% -显示出显着的序列相似性 与目前数据库中的其他蛋白质相比，约70%的蛋白质在 至少在远亲细菌的水平上，大约40%含有 在真核生物或微生物蛋白中保守的区域。 90%以上 急诊大肠杆菌蛋白质，无论是功能信息，或显着 序列相似性或两者都可用。 约46%的E.杆菌 蛋白质属于286簇种内同源物（旁系同源物） 定义为具有显著的成对相似性。 另外10%可能是 包括在簇中，使用敏感的方法检测保守的基序。 大多数集群只有两到四个成员。 在 相反，近25%的E.大肠杆菌蛋白质属于四个最大的 paralogs类 这些类别包括渗透酶; ATP酶和ATP酶。 具有保守的“Walker型”基序的GTP酶;螺旋-转角-螺旋 调节蛋白;和二核苷酸结合蛋白。 基因编码 旁系同源蛋白质沿染色体非随机沿着分布。 与E.大肠杆菌蛋白质允许预测 一些重要的真核基因的可能功能，包括 几家公司的产品与人类疾病有关。 我们的结论 细菌的蛋白质序列通常是高度保守的 发展，并与目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的信息， 细菌基因组中绝大多数基因的功能。 的 该项目的意义在于制定一项战略， 在基因组规模上对蛋白质序列进行比较分析。

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.