Rare creation of recombinant mtDNA haplotypes in mammalian tissues
Rare creation of recombinant mtDNA haplotypes in mammalian tissues
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DOI：
10.1073/pnas.0408666102
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发表时间：
2005-04-26
影响因子：
11.1
通讯作者：
Hayashi, JL
中科院分区：
文献类型：
--
作者：
Sato, A;Nakada, K;Hayashi, JL
重组mtDNA是否能在哺乳动物细胞中产生的问题多年来一直存在争议。我们通过分离人类体细胞杂交细胞和产生携带两种不同mtDNA单倍型的小鼠，为非常罕见的重组mtDNA单倍型的产生提供了令人信服的证据。为了避免将PCR跳跃产物误解为重组体，我们使用纯化的rntDNA进行克隆和测序。结果表明，从小鼠组织中纯化的318个mtDNA克隆中，只有3个与重组mtDNA单倍型相对应，而在人类体细胞杂种细胞中未发现重组mtDNA单倍型。如此极低的mtDNA重组频率并不需要对基于其缺失的人类进化的重要概念进行任何修改。考虑到mtDNA周围高浓度的活性氧及其频繁的链断裂，重组克隆将对应于通过修复核苷酸错配产生的基因转换产物。
The problem of whether recombinant mtDNAs are created in mammalian cells has been controversial for many years. We show convincing evidence for the very rare creation of recombinant mtDNA haplotypes by isolating human somatic hybrid cells and by generating mice carrying two different mtDNA haplotypes. To avoid misinterpretation of PCR-jumping products as recombinants, we used purified rntDNAs for cloning and sequencing. The results showed that only three of 318 clones of mtDNA purified from mouse tissues corresponded to recombinant mtDNA haplotypes, whereas no recombinants were found in human somatic hybrid cells. Such an extremely low frequency of mtDNA recombination does not require any revision of important concepts on human evolution that are based on its absence. Considering the high concentration of reactive oxygen species around the mtDNA and its frequent strand breakage, recombinant clones would correspond to gene conversion products created by repair of nucleotide mismatches.