Detection of single nucleotide variants in the mitochondrial genome of healthy mice and humans

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Single nucleotide mutations in the mitochondrial genome are linked to aging in humans, primates, and rodents and cause neuromuscular diseases in humans. Load of mitochondrial variants in healthy tissues, however, is little known. Employing an unbiased detection method with no prior enzymatic amplification, we observed that the mitochondrial genome of embryonic, adult, and aged mouse brain from two different strains contains a diversity of single nucleotide variants with no age-related increase in abundance. We also observed de novo variants in single oocytes and adult liver arising at 5x10−5 and 8x10−6 substitutions per base pair per generation, respectively. Moreover, we found variants in human placenta of healthy donors that may reach up to 66% of all mitochondrial genome copies. Increase in the heteroplasmy of the variants observed in healthy mouse and human tissues and of those arisen de novo at high frequency in mice may lead to mitochondrial dysfunction and disease.