Heteroplasmy
[3] Very low-level heteroplasmic variance is present in essentially all individuals, even those who are healthy, and is likely to be due to both inherited and somatic single base substitutions.
[5] The distinction of microheteroplasmy and more gross heteroplasmy is dictated by technical considerations - classical DNA sequencing of mitochondrial DNA 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 work of Lin et al.[6] 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 copy of mitochondrial DNA has on average 3.3 mutations changing protein structure.
The discovery of microheteroplasmy lends support to the mitochondrial theory of aging, and has already been linked to the causation of Parkinson's disease.
[7] In 1909, while studying chloroplast genomes, Erwin Baur made the first observations about organelle inheritance patterns.
[8] Entities undergoing uniparental inheritance and with little to no recombination may be expected to be subject to Muller's ratchet, the inexorable accumulation of deleterious mutations until functionality is lost.
[13] The mitochondrial bottleneck concept refers to the classic evolutionary term, which is used to explain an event that reduces and specifies a population.
Consequently, when paired with a high degree of replication, a rare or mutated allele can begin to proportionally dominate.
[14] Selective differences between naturally occurring mtDNA types may pose challenges for gene therapies.
Because each cell contains thousands of mitochondria, nearly all organisms house low levels of mitochondrial variants, conferring some degree of heteroplasmy.
Although a single mutational event might be rare in its generation, repeated mitotic segregation and clonal expansion can enable it to dominate the mitochondrial DNA pool over time.
Preimplantation genetic screening (PGS) can be used to quantitate the risk of a child of being affected by a mitochondrial disease.
