Mitochondrial DNA rearrangements: intracellular information system.

The extent of mtDNA rearrangements has been analyzed in nDNA preparations of rat and human with a statistically representative group of oligonucleotides directed to two regions of mtDNA: genes for cytochrome oxidase subunits I and III. Human PCR preparations generated with oligonucleotides directed 'normally' showed the expected fragment for mtDNA and the presence of a plethora of fragments with rearrangements (deletions and insertions), in contrast to rat PCR preparations under the same reaction conditions in which these kinds of rearranged fragments were rarely observed. Both human and rat PCR preparations generated with oligonucleotides directed 'inversely' showed numerous fragments, some of which showed differences in copy number correlating with distinct phases during development/aging. Sequence analysis of some normal and rearranged fragments demonstrated in all cases DNA sequences 99% homologous with other mtDNA sequences at rearranged fragments. No evidence of nuclear DNA sequences was found. The following scheme is proposed for mtDNA rearrangements during the lifetime of an organism: variation in copy number of some fragments with inversions of mtDNA depends on the specific developmental/aging period; in old cells there is an increase in higher molecular weight mtDNA deletions. These findings strongly suggest that the mtDNA rearrangements play a role as an intracellular 'information system'.