MARKED REPLICATIVE ADVANTAGE OF HUMAN MTDNA CARRYING A POINT MUTATION THAT CAUSES THE MELAS ENCEPHALOMYOPATHY
MARKED REPLICATIVE ADVANTAGE OF HUMAN MTDNA CARRYING A POINT MUTATION THAT CAUSES THE MELAS ENCEPHALOMYOPATHY
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DOI：
10.1073/pnas.89.23.11164
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发表时间：
1992-12-01
影响因子：
11.1
通讯作者：
ATTARDI, G
中科院分区：
文献类型：
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作者：
YONEDA, M;CHOMYN, A;ATTARDI, G
通过将具有MELAS脑肌病相关mtDNA突变（MELAS是线粒体肌病、脑病、乳酸酸中毒和中风样发作）的四个家系个体的线粒体转移到人类mtDNA缺失（rh度）细胞中，构建了转化子，研究了突变型和野生型mtDNA的分离。在13个含有野生型和突变型mtdna混合物的克隆细胞系中，有5个发现其基因型向纯突变型快速转变。其他8个细胞系，包括6个mtDNA几乎同质突变的细胞系，则保持了稳定的基因型。亚克隆实验和生长速率测量清楚地表明，突变体mtDNA的细胞内复制优势是在不稳定细胞系中观察到的突变基因型的显著转变的主要原因。
The segregation of mutant and wild-type mtDNA was investigated in transformants constructed by transferring human mitochondria from individuals belonging to four pedigrees with the MELAS encephalomyopathy-associated mtDNA mutation (MELAS is mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) into human mtDNA-less (rho-degrees) cells. Five of 13 clonal cell lines containing mixtures of wild-type and mutant mtDNAs were found to undergo a rapid shift of their genotype toward the pure mutant type. The other 8 cell lines, which included 6 exhibiting nearly homoplasmic mutant mtDNA, on the contrary, maintained a stable genotype. Subcloning experiments and growth rate measurements clearly indicated that an intracellular replicative advantage of mutant mtDNA was mainly responsible for the dramatic shift toward the mutant genotype observed in the unstable cell lines.