Evolution of cell-to-cell variability in stochastic, controlled, heteroplasmic mtDNA populations

Populations of physiologically vital mitochondrial DNA (mtDNA) molecules evolve in cells under control from the nucleus. The evolution of populations of mixed mtDNA types is complicated and poorly understood, and variability of these controlled admixtures plays a central role in the inheritance and onset of genetic disease. Here, we develop a mathematical theory describing the evolution and variability in these stochastic populations for any type of cellular control, showing that cell-to-cell variability in mtDNA, and mutant load, inevitably increases with time, according to rates which we derive and which are notably independent of the mechanistic details of feedback signalling. We show wit