Yoneda M, Chomyn A, Martinuzzi A, Hurko O, Attardi G
Division of Biology, California Institute of Technology, Pasadena 91125.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11164-8. doi: 10.1073/pnas.89.23.11164.
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 0) 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.
通过将来自四个患有与线粒体脑肌病伴乳酸血症和卒中样发作（MELAS，即线粒体肌病、脑病、乳酸酸中毒和卒中样发作）相关的线粒体DNA突变的家系个体的人类线粒体转移到无人类线粒体DNA（ρ0）的细胞中构建转化体，研究了突变型和野生型线粒体DNA的分离情况。在13个含有野生型和突变型线粒体DNA混合物的克隆细胞系中，有5个被发现其基因型迅速向纯突变型转变。相反，其他8个细胞系，包括6个几乎为纯质突变型线粒体DNA的细胞系，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，突变型线粒体DNA在细胞内的复制优势是导致不稳定细胞系中观察到的向突变基因型急剧转变的主要原因。
