The large majority of mitochondrial DNA (mtDNA) deletions analyzed from 
mitochondrial myopathies and aging humans have been found to be flanked by 
direct repeats, a finding which has led to the slip-replication hypothesis of 
deletion formation. In this study, we have characterized 13 mtDNA deletion 
breakpoints from skeletal muscle harvested from 9- to 27-year-old rhesus 
monkeys. Seven of the deletions, five of which were unique to a particular 
animal, did not have direct repeats at the deletion breakpoints. In contrast, 
two of the three deletions common to several animals had direct repeats flanking 
the breakpoints. It appears, therefore, that at least two different mechanisms 
exist by which mtDNA deletions are formed during aging, one requiring and one 
independent of flanking direct repeats. Furthermore, the species in which mtDNA 
deletions are detected may determine which mechanism predominates.