A model for damage load and its implications for the evolution of bacterial aging

Deleterious mutations appearing in a population increase in frequency until stopped by natural selection. The ensuing equilibrium creates a stable frequency of deleterious mutations or the mutational load. Here I develop the comparable concept of a damage load, which is caused by harmful non-heritable changes to the phenotype. A damage load also ensues when the increase of damage is opposed by selection. The presence of a damage load favors the evolution of asymmetrical transmission of damage by a mother to her daughters. The asymmetry is beneficial because it increases fitness variance, but it also leads to aging or senescence. A mathematical model based on microbes reveals that a cell lineage dividing symmetrically is immortal if lifetime damage rates do not exceed a threshold. The evolution of asymmetry allows the lineage to persist above the threshold, but the lineage becomes mortal. In microbes with low genomic mutation rates, it is likely that the damage load is much greater than the mutational load. In metazoans with higher genomic mutation rates, the damage and the mutational load could be of the same magnitude. A fit of the model to experimental data shows that Escherichia coli cells experience a damage rate that is below the threshold and are immortal under the conditions examined. The model estimates the asymmetry level of E. coli to be low but sufficient for persisting at higher damage rates. The model also predicts that increasing asymmetry results in diminishing fitness returns, which may explain why the bacterium has not evolved higher asymmetry.
Author Summary Almost all living organisms deteriorate with time through the process of aging or senescence. Because most studies on senescence examined organisms possessing a juvenile state, it was thought that bacteria, which reproduce by producing two apparently identical daughter cells, were immortal and not senescent. Recent studies have demonstrated that bacteria senesce because one daughter is allocated a larger share of the mother's load of non-genetic damage. Nonetheless, it is still equivocal whether bacterial senescence renders them mortal. I have developed a model that demonstrates that bacteria can be immortal if they experience damage below a threshold rate. A fit of the model to data shows that bacteria grown under standard laboratory conditions are immortal because they encounter a rate below the threshold. Because bacteria often experience higher damage rates in nature, it is likely that bacteria are generally mortal. The allocation of more damage to one daughter and the resulting mortality is the price bacteria pay to survive higher damage rates. These results suggest that senescence originated with the evolution of the first single-celled organisms and that it is ancestral in all multicellular organisms.