Evolution of DNA polymerases: an inactivated polymerase-exonuclease module in Pol epsilon and a chimeric origin of eukaryotic polymerases from two classes of archaeal ancestors.

Evolution of DNA polymerases: an inactivated polymerase-exonuclease module in Pol epsilon and a chimeric origin of eukaryotic polymerases from two classes of archaeal ancestors.
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DOI:
10.1186/1745-6150-4-11
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发表时间:
2009-03-18
期刊:
影响因子:
5.5
通讯作者:
Koonin EV
Koonin EV
中科院分区:
生物学2区
文献类型:
--
作者:
Tahirov TH;Makarova KS;Rogozin IB;Pavlov YI;Koonin EV

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DNA聚合酶是DNA复制和修复的关键酶,它的进化是细胞生命历史重建的核心。然而,古生菌和真核生物的DNA聚合酶之间的进化关系的细节仍然没有得到解决。我们进行了古细菌,真核生物和细菌的B-家族DNA聚合酶,这是在古细菌和真核生物中的主要复制聚合酶,结合结构域架构的分析比较分析。令人惊讶的是,我们发现真核生物聚合酶ε由两个串联的核酸外切酶-聚合酶模块组成,即活性N-末端模块和C-末端模块,其中两个酶结构域均失活。这两个模块彼此之间的关系很远,这一观察结果表明,Pol ε的进化可能是由于C-末端锌指上游的一种不同的聚合酶的插入和随后的失活,而不是串联复制。Pol ε中失活的核酸外切酶-聚合酶模块的存在与古细菌B家族聚合酶的不同家族中两个酶结构域的类似失活平行。系统发育分析结果表明,真核生物B家族聚合酶很可能起源于两种亲缘关系较远的古细菌B家族聚合酶,其中一种形式产生Pol ε,另一种形式产生Pol α、Pol δ和Pol ε的共同祖先。出乎意料地,存在于所有真核生物B家族聚合酶中的C末端Zn指与古细菌D家族DNA聚合酶的Zn指同源,而古细菌D家族DNA聚合酶在其他方面与B家族无关。Polε的锌指与古细菌PolD中的对应物的相似性明显大于其他真核生物B家族聚合酶的锌指。真核生物DNA聚合酶的进化似乎涉及了以前未被注意的复杂事件。我们假设真核生物的古祖先编码三种DNA聚合酶,即两种不同的B-家族聚合酶和一种D-家族聚合酶,所有这些都有助于真核生物复制机制的进化。锌指可能是在真核生物发生之前或过程中通过B家族形式从PolD获得的,该B家族形式产生Pol ε,随后被其他B家族真核生物聚合酶的祖先捕获。Pol ε的失活聚合酶-外切核酸酶模块可能是通过与不同的聚合酶融合而进化的,而不是通过Pol ε的活性模块的复制,并且可能在真核复制和修复复合物的组装中发挥重要作用。本文由帕特里克·福特尔、Arcady Mushegian和Chris Ponting审阅。有关完整的评论,请访问评论者报告部分。
Evolution of DNA polymerases, the key enzymes of DNA replication and repair, is central to any reconstruction of the history of cellular life. However, the details of the evolutionary relationships between DNA polymerases of archaea and eukaryotes remain unresolved. We performed a comparative analysis of archaeal, eukaryotic, and bacterial B-family DNA polymerases, which are the main replicative polymerases in archaea and eukaryotes, combined with an analysis of domain architectures. Surprisingly, we found that eukaryotic Polymerase ε consists of two tandem exonuclease-polymerase modules, the active N-terminal module and a C-terminal module in which both enzymatic domains are inactivated. The two modules are only distantly related to each other, an observation that suggests the possibility that Pol ε evolved as a result of insertion and subsequent inactivation of a distinct polymerase, possibly, of bacterial descent, upstream of the C-terminal Zn-fingers, rather than by tandem duplication. The presence of an inactivated exonuclease-polymerase module in Pol ε parallels a similar inactivation of both enzymatic domains in a distinct family of archaeal B-family polymerases. The results of phylogenetic analysis indicate that eukaryotic B-family polymerases, most likely, originate from two distantly related archaeal B-family polymerases, one form giving rise to Pol ε, and the other one to the common ancestor of Pol α, Pol δ, and Pol ζ. The C-terminal Zn-fingers that are present in all eukaryotic B-family polymerases, unexpectedly, are homologous to the Zn-finger of archaeal D-family DNA polymerases that are otherwise unrelated to the B family. The Zn-finger of Polε shows a markedly greater similarity to the counterpart in archaeal PolD than the Zn-fingers of other eukaryotic B-family polymerases. Evolution of eukaryotic DNA polymerases seems to have involved previously unnoticed complex events. We hypothesize that the archaeal ancestor of eukaryotes encoded three DNA polymerases, namely, two distinct B-family polymerases and a D-family polymerase all of which contributed to the evolution of the eukaryotic replication machinery. The Zn-finger might have been acquired from PolD by the B-family form that gave rise to Pol ε prior to or in the course of eukaryogenesis, and subsequently, was captured by the ancestor of the other B-family eukaryotic polymerases. The inactivated polymerase-exonuclease module of Pol ε might have evolved by fusion with a distinct polymerase, rather than by duplication of the active module of Pol ε, and is likely to play an important role in the assembly of eukaryotic replication and repair complexes. This article was reviewed by Patrick Forterre, Arcady Mushegian, and Chris Ponting. For the full reviews, please go to the Reviewers' Reports section.
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