Ultra-Deep Sequencing of Mouse Mitochondrial DNA: Mutational Patterns and Their Origins

Ameur A, Stewart JB, Freyer C, Hagström E, Ingman M, et al. (2011) Ultra-Deep Sequencing of Mouse Mitochondrial DNA: Mutational Patterns and Their Origins. PLoS Genet 7(3): e1002028. doi:10.1371/journal.pgen.1002028

Mitochondria represent the powerhouses of cells and have their own DNA. Mutations in the mitochondrial genome are associated with a range of human diseases and have also been implicated as a driving force behind the aging process. The authors of this study used ultra-deep sequencing to study the genome-wide mutation load in the mitochondrial DNA (mtDNA) of liver from normal inbred mice and mice that express a proof-reading–deficient mtDNA polymerase (mtDNA mutator mice) that cause premature aging. The mtDNA mutator mice show a dramatic increase of point mutations with age and have 10-times-higher point mutation levels than wildtype siblings or normal C57Bl/6N mice. Circular mtDNA molecules with large deletions occur at very low frequencies in mtDNA mutator mice and are therefore unlikely to contribute to the premature aging phenotype. The study found no increase in levels of point mutations or deletions in normal mice with increasing age, arguing against the accumulation of mtDNA mutations as contributing to aging. These results indicate that most somatic mtDNA mutations occur as replication errors during the rapid amplification of mtDNA during embryogenesis and do not result from damage accumulation in adult life.