Variation in mitochondrial DNA (mtDNA) – the genetic material of the cell’s energy factories – impacts human characteristics and disease. Current models posit that mtDNA variation within an individual (called heteroplasmy) results from inherited or random spontaneous mutations.
To test these models, David Samuels, Ph.D., Chun Li, Ph.D., and colleagues sequenced the mtDNA in the same ten tissues from unrelated individuals.
They were surprised to find that certain tissues – kidney, liver and skeletal muscle – had identical recurrent mutations in the unrelated individuals that were not detected in other tissues. The recurrent mutations occurred in or near sites that regulate mtDNA replication, suggesting that the variations alter replication dynamics.
The findings, reported Nov. 7 in PLOS Genetics, suggest a completely different model of mtDNA heteroplasmy – one in which a non-random process results in particular mutations, but only in specific tissues. The mutations, the researchers suggest, may result from tissue-specific positive selection because they offer advantages to mtDNA replication.
This research was supported by grants from the National Institutes of Health (HG004517, AG036445, GM073744).
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