Stochastic survival of the densest and mitochondrial DNA clonal expansion in aging

Clonal spread of DNA mutations is a fundamental phenomenon in both evolution and aging. High levels of mitochondrial DNA mutations are linked to muscle weakness in aging, which has a knock-on effect on overall health, contributing to mounting pressures on health care systems. For decades, scientists have asked how mitochondrial DNA harboring deleterious mutations can expand in skeletal muscle fibers. We provide evidence that this expansion could be driven by an unusual evolutionary mechanism, requiring only noise (stochasticity), a higher density of mutants, and a system with spatial structure. Critically, mutants need not replicate faster. This mechanism, that we have termed stochastic survival of the densest, can yield traveling waves of mutants, with potential applications in a range of evolutionary models.