| Autor: |
Biba DA; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.; Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA., Wolf YI; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA., Koonin EV; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA., Rochman ND; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.; Institute for Implementation Science in Population Health (ISPH), City University of New York (CUNY), New York, NY, USA.; Department of Epidemiology and Biostatistics, Graduate School of Public Health and Health Policy, City University of New York (CUNY), New York, NY, USA. |
| Abstrakt: |
Over the course of multiple divisions, cells accumulate diverse non-genetic, somatic damage including misfolded and aggregated proteins and cell wall defects. If the rate of damage accumulation exceeds the rate of dilution through cell growth, a dedicated mitigation strategy is required to prevent eventual population collapse. Strategies for somatic damage control can be divided into two categories, asymmetric allocation and repair, which are not, in principle, mutually exclusive. Through mathematical modelling, we identify the optimal strategy, maximizing the total cell number, over a wide range of environmental and physiological conditions. The optimal strategy is primarily determined by extrinsic (damage-independent) mortality and the physiological model for damage accumulation that can be either independent (linear) or increasing (exponential) with respect to the prior accumulated damage. Under the linear regime, the optimal strategy is either exclusively repair or asymmetric allocation whereas under the exponential regime, the optimal strategy is mixed. Repair is preferred when extrinsic mortality is low, whereas at high extrinsic mortality, asymmetric damage allocation becomes the strategy of choice. We hypothesize that optimization over somatic damage repair and asymmetric allocation in early cellular life forms gave rise to the r and K selection strategies. |
