Mitochondrial mutational spectra in human cells and tissues
Mitochondrial mutational spectra in human cells and tissues
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DOI：
10.1073/pnas.94.25.13798
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Thilly, WG
中科院分区：
文献类型：
--
作者：
Khrapko, K;Coller, HA;Thilly, WG
我们发现，结肠、肺和肌肉等人体器官及其衍生肿瘤几乎都具有所有线粒体热点点突变。在碱基对 10,030-10,130 的线粒体序列中已鉴定出 17 个热点，主要是 G --> A 和 A --> G 转变。在人类 IS 细胞系 TK6 中，突变比例随着细胞代数的增加而增加，表明它们是可遗传的变化。 TK6 细胞和人体组织中线粒体点突变率似乎比核点突变率高两个数量级以上。体内和体外热点集的相似性使我们得出结论，所研究的序列中的人类线粒体点突变主要是自发的，并且是由 DNA 复制错误或 DNA 与内源代谢物的反应引起的。这段短序列中过渡突变的主导地位和大量热点类似于体外 DNA 聚合酶产生的光谱。
We have found that human organs such as colon, lung, and muscle, as well as their derived tumors, share nearly all mitochondrial hotspot point mutations. Seventeen hotspots, primarily G --> A and A --> G transitions, have been identified in the mitochondrial sequence of base pairs 10,030-10,130. Mutant fractions increase with the number of cell generations in a human IS cell line, TK6, indicating that they are heritable changes. The mitochondrial point mutation rate appears to he more than two orders of magnitude higher than the nuclear point mutation rate in TK6 cells and in human tissues. The similarity of the hotspot sets in vivo and in vitro leads us to conclude that human mitochondrial point mutations in the sequence studied are primarily spontaneous in origin and arise either from DNA replication error or reactions of DNA with endogenous metabolites. The predominance of transition mutations and the high number of hotspots in this short sequence resembles spectra produced by DNA polymerases in vitro.