A phylogenomic study of the MutS family of proteins

A phylogenomic study of the MutS family of proteins
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DOI:
10.1093/nar/26.18.4291
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发表时间:
1998-09-15
影响因子:
14.9
通讯作者:
Eisen, JA
Eisen, JA
中科院分区:
生物学2区
文献类型:
--
作者:
Eisen, JA

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大肠杆菌的MutS蛋白在DNA复制过程中的错误识别和修复中起着关键作用,MutS的同源物已在许多物种中发现,包括真核生物,细菌和其他细菌,这些蛋白一起被归类为MutS家族。虽然这些蛋白质中的许多与大肠杆菌MutS具有相似的活性,但MutS家族成员之间存在显著的功能多样性。这种多样性甚至在物种内也可以看到;许多物种编码具有不同功能的多个MutS同源物。为了更好地表征MutS蛋白家族,我使用了系统发育重建和完整基因组序列分析的组合。该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的亚家族。这些直系同源物在特定物种中的分布的分析和亚家族内和亚家族之间的关系的检查用于鉴定MutS家族历史中可能的进化事件(例如,基因复制、横向转移和基因丢失)。特别是,有证据表明,在生命进化的早期基因复制导致两个主要的MutS谱系,一个包括已知的蛋白质在错配修复和其他包括已知的蛋白质在染色体分离和交叉的功能。MutS家族的推断进化历史用于预测分析中包含的一些未表征的基因和物种。例如,由于功能通常在亚家族和谱系中是保守的,因此提出可以通过它们在MutS家族树中的位置来预测未表征的蛋白质的功能。利用基因组学的方法来研究基因和基因组进行了讨论。
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.