TY - JOUR T1 - The adaptive potential of non-heritable somatic mutations JF - bioRxiv DO - 10.1101/2021.04.30.442123 SP - 2021.04.30.442123 AU - Paco Majic AU - E. Yagmur Erten AU - Joshua L. Payne Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/30/2021.04.30.442123.abstract N2 - Non-heritable somatic mutations are typically associated with deleterious effects such as in cancer and senescence, so their role in adaptive evolution has received little attention. However, most somatic mutations are harmless and some even confer a fitness advantage to the organism carrying them. We hypothesized that heritable, germline genotypes that are likely to express an advantageous phenotype via non-heritable somatic mutation will have a selective advantage over other germline genotypes, and this advantage will channel evolving populations toward more fit germline genotypes, thus promoting adaptation. We tested this hypothesis by simulating evolving populations of developing organisms with an impermeable germline-soma separation navigating a minimal fitness landscape. The simulations revealed the conditions under which non-heritable somatic mutations promote adaptation. Specifically, this can occur when the somatic mutation supply is high, when only very few cells with the advantageous somatic mutation are required to increase organismal fitness, and when the somatic mutation also confers a selective advantage to cells with that mutation. We therefore provide proof-of-principle that non-heritable somatic mutations can promote adaptive evolution via a process we call somatic genotypic exploration. We discuss the biological plausibility of this phenomenon, as well as its evolutionary implications.Significance The immensity of non-heritable genetic diversity arising in the soma has been largely disregarded in evolutionary theory as a source of adaptation. Here, we introduce a model in which non-heritable somatic mutations arising during development confer an organismal fitness advantage. Analysis of this model shows how such mutations channel evolving populations toward adaptive germline genotypes. This is most likely to occur when somatic mutations confer a fitness benefit at both the cellular and organismal levels, evoking a synergistic form of multi-level selection that contrasts with the antagonistic forms typically associated with somatic mutations in cancer and senescence. As such, our study invites a new view of somatic genetic diversity in evolutionary theory as a potential source of adaptation.Competing Interest StatementThe authors have declared no competing interest. ER -