Origin, transmission, and segregation of mitochondrial DNA dimers in mouse hybrid and cybrid cell lines.

Hybrid and cybrid progeny lines were constructed from mouse LA9 cells which contain almost exclusively mtDNA monomers and LDTK cells which contain only unicircular mtDNA dimers. The proportion of mtDNA monomers and dimers in the progeny lines was determined both as a function of the number of population doublings since fusion and of selection for expression of a mutant phenotype encoded on one of the parental mtDNAs. There was no preferential segregation of either parental mtDNA in early-passage progeny lines, irrespective of whether or not selection was applied. In marked contrast, there was an accumulation of mtDNA dimers in late-passage progeny lines maintained in the absence of selection for a drug-resistance marker carried by the parental mtDNA monomers. When such selection was applied, roughly equal mass proportions of both parental mtDNAs were maintained in most lines. However, in several progeny lines, new types of mtDNA dimers carrying the selected resistance marker initially encoded in the monomeric mtDNA were present. In some of these latter lines, the new mtDNA dimers apparently arose from LA9 monomers, possibly by recombination. It is hypothesized that mammalian mitochondria normally have a recombination system which maintains low steady-state levels of mtDNA unicircular oligomers by preferentially resolving dimers into two monomers.