The rate of mitochondrial mutagenesis is faster in mice than humans

Endi Wang, Alice Wong, Gino A Cortopassi

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

We have investigated mitochondrial DNA (mtDNA) mutagenesis in the laboratory mouse. Using a nested PCR method for quantification, the absolute frequency, tissue distribution and rate of increase of mitochondrial deletion mutations was determined. Multiple deletions arise in brain, cardiac muscle and kidney tissues; deletions occur most frequently at regions of directly repeated mtDNA homology. Deletion frequencies rose by 2.5 x 105, 6300- and 4000-fold in heart, brain and kidney, respectively, between young and old mice. The rates of mtDNA mutation accumulation in mouse and human hearts are modeled well by exponential equations, with r-values of 0.96 and 0.97, and mutations rose much faster in mouse than human mtDNA per unit time. Thus, maintenance of the human mitochondrial genome is much better than that of mice, consistent with the higher rate and final extent of total DNA repair in humans than mice, that has been observed by others and consistent with the predictions of the disposable soma model of aging. A comparison of mtDNA mutagenesis from cardiocytes vs. whole heart tissue was undertaken. Deletion mutations were observed to be 100-fold lower in DNA prepared from isolated cardiocytes than from whole heart homogenates, consistent with a model of uneven mtDNA mutation accumulation.

Original languageEnglish (US)
Pages (from-to)157-166
Number of pages10
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume377
Issue number2
DOIs
StatePublished - Jul 1997

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Mitochondrial DNA
Mutagenesis
Sequence Deletion
Kidney
Mitochondrial Genome
Brain
Carisoprodol
Human Genome
Tissue Distribution
DNA Repair
Myocardium
Muscles
Polymerase Chain Reaction
Mutation
DNA

Keywords

  • Aging
  • Comparative
  • DNA repair
  • Mitochondrial
  • Mouse
  • Mutagenesis

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

The rate of mitochondrial mutagenesis is faster in mice than humans. / Wang, Endi; Wong, Alice; Cortopassi, Gino A.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 377, No. 2, 07.1997, p. 157-166.

Research output: Contribution to journalArticle

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