A cell contains numerous mitochondria, and each mitochondrion contains dozens of copies of the mitochondrial genome. Furthermore, the mitochondrial genome has a higher mutation rate (approximately 100 times higher) than the nuclear genome. This results in a heterogeneous population of mitochondrial DNA within the same cell and even within the same mitochondria;. Therefore, mitochondria are considered heteroplasmic. When a cell divides, its mitochondria divide between the two daughter cells. However, the mitochondrial segregation process is random and much less organized than the highly precise process of nuclear chromosome segregation during mitosis. As a result, daughter cells receive similar, but not identical, copies of their mitochondrial DNA.

 Why do mitochondria have such a high mutation rate? A nuclear gene called DNA polymerase gamma (POLG) encodes DNA polymerase, which is responsible for replicating the mitochondrial genome. The POLG protein consists of two domains: a catalytic domain that exhibits polymerase activity and an exonuclease domain that participates in the detection and elimination of DNA base pair mismatches that occur during DNA replication. A recent study suggests that mitochondria may have a nucleotide imbalance leading to lower POLG fidelity and higher rates of mitochondrial DNA mutation.

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