Repeats, longevity and the sources of mtDNA deletions: evidence from ‘deletional spectra’

Perfect direct repeats and, in particular, the prominent 13 bp repeat, are thought to cause mitochondrial DNA (mtDNA) deletions, which have been associated with the aging process. Accordingly, individuals lacking the 13 bp repeat are highly prevalent among centenarians and overall number of perfect repeats in mammalian mitochondrial genomes negatively correlates with species’ longevity. However, detailed examination of the distribution of mtDNA deletions challenges a special role of the 13 bp repeat in generating mtDNA deletions. Instead, deletions appear to depend on long and stable, albeit imperfect, duplexes between distant mtDNA segments. Furthermore, significant dissimilarities in breakpoint distributions suggest that multiple mechanisms are involved in creating mtDNA deletions.