Митохондриялық ДНК және гомоплазма: зерттеулер мен ауруларға қатысы

Identity of organellar DNA sequences in a cell

Homoplasmy is a term used in genetics to describe a eukaryotic cell whose copies of mitochondrial DNA are all identical. In normal and healthy tissues, all cells are homoplasmic. Homoplasmic mitochondrial DNA copies may be normal or mutated; (only occurring in some copies of mitochondrial DNA). It has been discovered, though, that homoplasmic mitochondrial DNA mutations may be found in human tumors. The term may also refer to uniformity of plant plastid DNA, whether occurring naturally or otherwise.

In almost every species, mitochondrial DNA is maternally inherited. Researchers also believe that this could be a by product of species hybridization. Many diseases resulting from mutations in mitochondrial DNA are not inherited but developed as the untranslated region of mitochondrial DNA (mtDNA) is thought to be particularly susceptible to mutation. Many cancer types are the result of mutations in the mtDNA. For example, a specific type of mutation in one specific area of mtDNA was found to be in several different tumor types. Mitochondria often undergo fission and fusion, which means that different organelles in the same cell can fuse together to become one mitochondria, or can break apart and become two. This process can be used to mitigate the effects of heteroplasmic mutations. Each mitochondria has multiple nucleoids, which consist of several copies of mtDNA, and when mitochondria fuse together, these nucleoids do not exchange DNA; therefore, if two mitochondria that have different DNA fuse together, they will have only two types of nucleoids. This means that fusion can be used to generate complementary nucleoids if a mutation causes one mitochondria to no longer be functional. Additionally, fission can cause one mitochondria with two different nucleoids to become two mitochondria each with only one type of nucleoid. Although it is passed down maternally, it is seen more often in young men than in other ages or sexes, which leads researchers to believe that there are many other genetic or environmental factors that contribute to developing the disease. Environmental factors, cigarette smoke in particular, have been shown to affect LHON's penetrance. In one study, cigarette smoke condensate was used to demonstrate the effects of smoking on cells with the LHON mutation. All cells were homoplasmic, but some were from individuals who were afflicted with LHON and some were from individuals who were just carriers. The researchers found that cigarette smoke condensate lowered the amount of mitochondria in the cells, but that carrier individuals were better able to compensate than those from individuals with LHON. Though there is an additive environmental effect, there is more to learn about why certain homoplasmic individuals have the disease and others do not.

Some research has shown that an inherited heteroplasmic mutation can cause cancer in older age as cells become homoplasmic. In one study, doctors found that a cancer patient's tumor consisted of only homoplasmic cells with mutant mtDNA and that healthy cells in his body were heteroplasmic for mutant mtDNA. Additionally, researchers found that the patient's siblings had the same heteroplasmic mutation. This indicates that the heteroplasmic mutation was inherited, and over time led to homoplasmic cells that caused cancer.