Mutagenesis by transient misalignment in the human mitochondrial DNA control region
Mutagenesis by transient misalignment in the human mitochondrial DNA control region
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DOI：
10.1046/j.1529-8817.2004.00099.x
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发表时间：
2004-07-01
影响因子：
1.9
通讯作者：
Rogozin, IB
中科院分区：
文献类型：
--
作者：
Malyarchuk, BA;Rogozin, IB
为了研究人类线粒体 DNA (mtDNA) 中的自发碱基替换，我们利用已发表的不同人群的多态性数据重建了高变片段 I 和 II (HVS I 和 II) 的突变谱。分类分析揭示了 HVS I 和 II 突变谱中的大量突变热点。统计分析表明，单调核苷酸运行中的链错位诱变在 mtDNA 控制区产生碱基取代中发挥着重要作用。 HVS I 区域中与引物链错位相容的突变频率几乎是模板链错位的两倍。在 HVS II 区域中，与引物和模板链错位模型相容的突变频率几乎相同。对链位错模型的进一步分析表明，根据L链序列重建的突变谱中过量的嘧啶转变是由L链嘧啶转变和H链嘌呤转变过量引起的。一般来说，在 HVS I 和 II 区域没有发现对亲本 H 链特异性位错诱变的显着偏向。
To study spontaneous base substitutions in human mitochondrial DNA (mtDNA), we reconstructed the mutation spectra of the hypervariable segments I and II (HVS I and II) using published data on polymorphisms from various human populations. Classification analysis revealed numerous mutation hotspots in HVS I and II mutation spectra. Statistical analysis suggested that strand dislocation mutagenesis, operating in monotonous runs of nucleotides, plays an important role in generating base substitutions in the mtDNA control region. The frequency of mutations compatible with the primer strand dislocation in the HVS I region was almost twice as high as that for template strand dislocation. Frequencies of mutations compatible with the primer and template strand dislocation models are almost equal in the HVS II region. Further analysis of strand dislocation models suggested that an excess of pyrimidine transitions in mutation spectra, reconstructed on the basis of the L-strand sequence, is caused by an excess of both L-strand pyrimidine transitions and H-strand purine transitions. In general, no significant bias toward parent H-strand-specific dislocation mutagenesis was found in the HVS I and II regions.