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Mitochondrial DNA

Human Mitochondrial Map


The mitochondrial DNA (mtDNA) is the product of the mitochondrion’s bacterial origin, and the mitochondria still retain separate systems to replicate and express the mtDNA genes. There are hundreds of mitochondria within each cell, and multiple mtDNAs within each mitochondrion. Hence, each cell contains thousands of mtDNAs outside of the nucleus. Since these mtDNAs are not associated with the chromosomes, they are not inherited from both the mother and father. Rather the mitochondria and mtDNAs are inherited through the egg cytoplasm, and thus are inherited exclusively from the mother (maternally-inherited). Moreover, since there are thousands of copies of the mtDNA in every cell, it is possible for a cell to harbor varying percentages of mutant and normal mtDNAs, ranging from all normal to partially mutant (a state known as heteroplasmy) to all mutant (homoplasmy). Hence, unlike nuclear genetic defects that result in stepwise biochemical deficiencies and hence stereotypical clinical symptoms, mtDNA defects vary in the degree of energy deficiency and hence the same mtDNA mutation can result in a wide range of energy differences with different associated symptoms.

The mtDNA has a very high mutation rate, between 10 to 100 times that of nuclear DNA (nDNA) genes. As a result, mtDNA diseases are probably very common. Indeed, even with own very limited knowledge of the nature and extent of mitochondrial diseases, it has been estimated that at least 1 in 9000 children are born with mitochondria-related diseases. Undoubtedly, however, this is a gross underestimation. It is already known that about 1% of all diabetes mellitus patients are the result of a single mtDNA mutation in the tRNALeu(UUR) gene at nucleotide pair (np) 3243, and that diabetes will affect about 10% of Western populations.

Originally, the mtDNA harbored several thousand genes, but today it contains only 37. The remainder of the original mtDNA genes were transferred to the nucleus during the first 2 billion years of the symbiosis, and are now scattered among the chromosomes in the nucleus. The nDNA encoded mitochondrial genes are expressed in the nucleus and cytosol, and the resulting proteins are transported back into the mitochondrion. Hence, the genetics of mitochondrial disease is highly complex. Mitochondrial defects can result from either mutations in the nDNA mitochondrial genes or the mtDNA mitochondrial genes. Moreover, since all of the genes necessary for mtDNA replication and expression are encoded by the nDNA, mutations in nDNA genes can result in the destruction of the mtDNA. This leads to a combination of nDNA and mtDNA inheritance patterns.