Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy.
- 1 December 1992
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 89 (23) , 11164-11168
- https://doi.org/10.1073/pnas.89.23.11164
Abstract
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.Keywords
This publication has 27 references indexed in Scilit:
- A point mutation in the mitochondrial tRNALeu(UUR) gene in melas (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes)Biochemical and Biophysical Research Communications, 1990
- Rapid shift in genotype of human mitochondrial DNA in a family with Leber's hereditary optic neuropathyBiochemical and Biophysical Research Communications, 1990
- Deletion mutants are functionally dominant over wild-type mitochondrial genomes in skeletal muscle fiber segments in mitochondrial diseaseCell, 1990
- Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutationCell, 1990
- Human Cells Lacking mtDNA: Repopulation with Exogenous Mitochondria by ComplementationScience, 1989
- Mitochondrial DNA mutations and neuromuscular diseaseTrends in Genetics, 1989
- Injection of mitochondria into human cells leads to a rapid replacement of the endogenous mitochondrial DNACell, 1988
- An extrachromosomal plasmid is the etiological precursor of kalDNA insertion sequences in the mitochrondrial chromosome of senescent neurosporaCell, 1986
- Transfection of human skeletal muscle cells with SV40 large T antigen gene coupled to a metallothionein promoterAnnals of Neurology, 1986
- Are mitochondrial structural genes selectively amplified during senescence in podospora anserina?Cell, 1982