High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection

High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection

The authors generated a model to track mitochondrial heteroplasmy in cells. They simulated mtDNA, which randomly accumulated mutations at each generation, according to a Poisson process. At cell division, each mtDNA molecule was randomly chosen and replicated, so that the total copy number of mtDNAs doubled from 5 to 10. The mtDNA molecules were then randomly, but equally, split between the two daughter cells. Following successive generations of this process, the authors found consistently that a macroscopic fraction of cells in the model would contain a homoplasmic mutation. This model argues against the idea that selection is required for homoplasmy to occur, which is sometimes thought to be the case in particular forms of cancer.