Knopf C W
Forschungsschwerpunkt Genomforschung und Bioinformatik, Deutsches Krebsforschungszentrum, Heidelberg, FRG.
Virus Genes. 1998;16(1):47-58. doi: 10.1023/a:1007997609122.
DNA viruses as their host cells require a DNA-dependent DNA polymerase (Pol) to faithfully replicate their genomic information. Large eukaryotic DNA viruses as well as bacterial viruses encode a specific Pol equipped with a proofreading 3'-5'-exonuclease, and other replication proteins. All known viral Pol belong to family A and family B Pol. Common to all viral Pol is the conservation of the 3'-5'-exonuclease domain manifested by the three sequence motifs Exo I, Exo II, and Exo III. The polymerase domain of family A and B Pol is clearly distinguishable. Family A Pol share 9 distinct consensus sequences, only two of them are convincingly homologous to sequence motif B of family B Pol. The putative sequence motifs A, B, and C of the polymerase domain are located near the C-terminus in family A Pol and more central in family B Pol. Thus, family A Pol show a significant greater spacing between the Exo III motif and the Pol motif A that is especially extended in the case of the mitochondrial Pol gamma. From each host and virus family whenever possible the consensus sequences of two distantly related polymerase species were aligned for assessment of phylogenetic trees, using both maximum parsimony and distance methods, and evaluated by bootstrap analysis. Three alternative methods yielded trees with identical major groupings. A subdivision of viral family B Pol was achieved resulting in a branch with Pol carrying out a protein-primed mechanism of DNA replication, including adenoviruses, bacteriophages and linear plasmids of plant and fungal origin. Archaebacterial Pol and cellular Pol epsilon were consistently found at the base of this branch. Another major branch comprised alpha- and delta-like viral Pol from mammalian herpesviruses, fish lymphocystis disease virus, insect ascovirus, and chlorella virus. Due to a lower branch integrity Pol of T-even bacteriophages, poxviruses, African swine fever virus, fish herpesvirus, and baculoviruses were not clearly resolved and placed in alternate groupings. A composite and rooted tree of family A and B Pol shows that viral Pol with a protein-priming requirement represent the oldest viral Pol species suggesting that the protein-primed mechanism is one of the earliest modes of viral DNA replication.
DNA病毒与其宿主细胞一样，需要一种依赖DNA的DNA聚合酶（Pol）来忠实地复制其基因组信息。大型真核DNA病毒以及细菌病毒都编码一种特定的Pol，该Pol配备有校对3'-5'-外切核酸酶和其他复制蛋白。所有已知的病毒Pol都属于A家族和B家族Pol。所有病毒Pol的共同之处在于3'-5'-外切核酸酶结构域的保守性，这由三个序列基序Exo I、Exo II和Exo III表现出来。A家族和B家族Pol的聚合酶结构域明显不同。A家族Pol共有9个不同的共有序列，其中只有两个与B家族Pol的序列基序B有令人信服的同源性。聚合酶结构域的假定序列基序A、B和C在A家族Pol中位于C末端附近，在B家族Pol中更靠近中心。因此，A家族Pol在Exo III基序和Pol基序A之间显示出明显更大的间距，在线粒体Polγ的情况下尤其如此。尽可能从每个宿主和病毒家族中选取两个远缘相关聚合酶物种的共有序列进行比对，以评估系统发育树，使用最大简约法和距离法，并通过自展分析进行评估。三种替代方法得到的树具有相同的主要分组。对病毒B家族Pol进行了细分，形成了一个分支，其中的Pol采用蛋白质引发的DNA复制机制，包括腺病毒、噬菌体以及植物和真菌来源的线性质粒。古细菌Pol和细胞Polε一直位于该分支的基部。另一个主要分支包括来自哺乳动物疱疹病毒、鱼类淋巴囊肿病病毒、昆虫痘病毒和小球藻病毒的α-和δ-样病毒Pol。由于T偶数噬菌体、痘病毒、非洲猪瘟病毒、鱼类疱疹病毒和杆状病毒的Pol分支完整性较低，它们没有被明确解析并被置于不同的分组中。A家族和B家族Pol的复合有根树表明，具有蛋白质引发需求的病毒Pol代表了最古老的病毒Pol物种，这表明蛋白质引发机制是病毒DNA复制的最早模式之一。
