Microheteroplasmy

Microheteroplasmy is a form of heteroplasmy, a type of mutational damage to mitochondrial DNA. While heteroplasmy in general includes mutations present in any fraction of mtDNA (from fractions of a percent to almost a hundred percent), microheteroplasmy is the presence of mutations levels of up to about 2 - 5 %. This distinction is dictated by technical considerations - classical DNA sequencing of mtDNA by the use of PCR is capable only of detecting mutations at levels of 10% or more, as a result of which mutations at lower levels were never systematically observed until the pioneering work of Lin et al [1].

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As it became apparent after the use of Lin's cloning and sequencing strategy, capable of detecting mutations at levels of 1% or less, such low-level heteroplasmy, or microheteroplasmy, is exceedingly common, and is in fact the most common form of mutational damage to human DNA found to date. In aged adults, each mtDNA copy has on average 3.3 mutations changing protein structure. This exceeds previous estimates by more than three orders of magnitude.

The discovery of microheteroplasmy lends support to the mitochondrial theory of aging, and has already been linked to the causation of Parkinson's disease[2].

References

• 1. Hum Mol Genet. 2002 Jan 15;11(2):133-45. High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain. Lin MT, Simon DK, Ahn CH, Kim LM, Beal MF. PMID 11809722
• 2. Biochem Biophys Res Commun. 2005 Jan 21;326(3):667-9. Mitochondrial ND5 mutations in idiopathic Parkinson's disease. Parker WD Jr, Parks JK. PMID 15596151
• Rejuvenation Res. 2005 Fall;8(3):172-98. Mitochondrial microheteroplasmy and a theory of aging and age-related disease. Smigrodzki RM, Khan SM. PMID 16144471