Eisen J A
Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
Nucleic Acids Res. 1998 Sep 15;26(18):4291-300. doi: 10.1093/nar/26.18.4291.
The MutS protein of Escherichia coli plays a key role in the recognition and repair of errors made during the replication of DNA. Homologs of MutS have been found in many species including eukaryotes, Archaea and other bacteria, and together these proteins have been grouped into the MutS family. Although many of these proteins have similar activities to the E.coli MutS, there is significant diversity of function among the MutS family members. This diversity is even seen within species; many species encode multiple MutS homologs with distinct functions. To better characterize the MutS protein family, I have used a combination of phylogenetic reconstructions and analysis of complete genome sequences. This phylogenomic analysis is used to infer the evolutionary relationships among the MutS family members and to divide the family into subfamilies of orthologs. Analysis of the distribution of these orthologs in particular species and examination of the relationships within and between subfamilies is used to identify likely evolutionary events (e.g. gene duplications, lateral transfer and gene loss) in the history of the MutS family. In particular, evidence is presented that a gene duplication early in the evolution of life resulted in two main MutS lineages, one including proteins known to function in mismatch repair and the other including proteins known to function in chromosome segregation and crossing-over. The inferred evolutionary history of the MutS family is used to make predictions about some of the uncharacterized genes and species included in the analysis. For example, since function is generally conserved within subfamilies and lineages, it is proposed that the function of uncharacterized proteins can be predicted by their position in the MutS family tree. The uses of phylogenomic approaches to the study of genes and genomes are discussed.
大肠杆菌的MutS蛋白在DNA复制过程中所产生错误的识别与修复方面发挥着关键作用。在包括真核生物、古细菌和其他细菌在内的许多物种中都发现了MutS的同源物，这些蛋白质共同被归入MutS家族。尽管这些蛋白质中的许多与大肠杆菌的MutS具有相似的活性，但MutS家族成员之间在功能上存在显著差异。这种差异甚至在物种内部也能看到；许多物种编码具有不同功能的多种MutS同源物。为了更好地描述MutS蛋白家族的特征，我结合了系统发育重建和对完整基因组序列的分析。这种系统基因组分析用于推断MutS家族成员之间的进化关系，并将该家族划分为直系同源物亚家族。通过分析这些直系同源物在特定物种中的分布以及研究亚家族内部和之间的关系，来确定MutS家族历史中可能的进化事件（如基因复制、横向转移和基因丢失）。特别是，有证据表明在生命进化早期的一次基因复制产生了两个主要的MutS谱系，一个包括已知在错配修复中起作用的蛋白质，另一个包括已知在染色体分离和交叉中起作用的蛋白质。推断出的MutS家族进化历史被用于对分析中包含的一些未表征基因和物种进行预测。例如，由于功能通常在亚家族和谱系内保守，因此有人提出可以通过未表征蛋白质在MutS家族树中的位置来预测其功能。本文还讨论了系统基因组方法在基因和基因组研究中的应用。
