Immortal DNA strand hypothesis

The immortal DNA strand hypothesis posits that adult stem cells replicate their DNA asymmetrically to minimize mutations in their genomes. It was proposed in 1975 by John Cairns as a mechanism that would benefit organisms by reducing cancer incidence. For decades, evidence for the hypothesis was sparse, contradictory and inconclusive.

Since the 2010s, evidence from a variety of species, including, mice, flies and humans, strongly suggests that DNA is randomly segregated in stem cells, thereby refuting the immortal strand hypothesis. Instead, multiple processes (xenobiotic metabolism, efflux, DNA repair and quiescence) are in place to minimize mutations, detrimental mutations are negatively selected and, in some cases, cells with driver mutations are kept in check by other cells by direct competition. Mechanisms such as these keep cancer rates low in humans, despite the fact that somatic mutagenesis is widespread and errors accumulate with age. In some stem cell compartments, such as the esophagus and hematopoietic stem cells, driver mutations are found in the majority of cells in older individuals.