Microheteroplasmy
Encyclopedia
In biology, microheteroplasmy is a form of heteroplasmy
, a type of mutation
al 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 work of Lin et al..
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
.
Heteroplasmy
Heteroplasmy is the presence of a mixture of more than one type of an organellar genome within a cell or individual...
, a type of mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
al damage to mitochondrial DNA
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...
. 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
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
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 work of Lin et al..
As it became apparent after the use of Lin's cloning
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...
and sequencing strategy, capable of detecting mutations at levels of 1% or less, such low-level heteroplasmy
Heteroplasmy
Heteroplasmy is the presence of a mixture of more than one type of an organellar genome within a cell or individual...
, 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
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
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
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
.
Further reading
- 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