Asymmetric Damage Segregation Constitutes an Emergent Population-Level Stress Response

TY - JOUR

T1 - Asymmetric Damage Segregation Constitutes an Emergent Population-Level Stress Response

AU - Vedel, Søren

AU - Nunns, Harry

AU - Košmrlj, Andrej

AU - Semsey, Szabolcs

AU - Trusina, Ala

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/8/24

Y1 - 2016/8/24

N2 - Asymmetric damage segregation (ADS) is a mechanism for increasing population fitness through non-random, asymmetric partitioning of damaged macromolecules at cell division. ADS has been reported across multiple organisms, though the measured effects on fitness of individuals are often small. Here, we introduce a cell-lineage-based framework that quantifies the population-wide effects of ADS and then verify our results experimentally in E. coli under heat and antibiotic stress. Using an experimentally validated mathematical model, we find that the beneficial effect of ADS increases with stress. In effect, low-damage subpopulations divide faster and amplify within the population acting like a positive feedback loop whose strength scales with stress. Analysis of protein aggregates shows that the degree of asymmetric inheritance is damage dependent in single cells. Together our results indicate that, despite small effects in single cell, ADS exerts a strong beneficial effect on the population level and arises from the redistribution of damage within a population, through both single-cell and population-level feedback.

AB - Asymmetric damage segregation (ADS) is a mechanism for increasing population fitness through non-random, asymmetric partitioning of damaged macromolecules at cell division. ADS has been reported across multiple organisms, though the measured effects on fitness of individuals are often small. Here, we introduce a cell-lineage-based framework that quantifies the population-wide effects of ADS and then verify our results experimentally in E. coli under heat and antibiotic stress. Using an experimentally validated mathematical model, we find that the beneficial effect of ADS increases with stress. In effect, low-damage subpopulations divide faster and amplify within the population acting like a positive feedback loop whose strength scales with stress. Analysis of protein aggregates shows that the degree of asymmetric inheritance is damage dependent in single cells. Together our results indicate that, despite small effects in single cell, ADS exerts a strong beneficial effect on the population level and arises from the redistribution of damage within a population, through both single-cell and population-level feedback.

U2 - 10.1016/j.cels.2016.06.008

DO - 10.1016/j.cels.2016.06.008

M3 - Journal article

C2 - 27426983

SN - 2405-4712

VL - 3

SP - 187

EP - 198

JO - Cell Systems

JF - Cell Systems

IS - 2

ER -