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.