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Asymmetric Damage Segregation Constitutes an Emergent Population-Level Stress Response

Vedel, Søren and Nunns, Harry and Košmrlj, Andrej and Semsey, Szabolcs and Trusina, Ala (2016) Asymmetric Damage Segregation Constitutes an Emergent Population-Level Stress Response. Cell Systems, 3 (2). pp. 187-198. ISSN 2405-4712.

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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.

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Additional Information:© 2016 Elsevier B.V. Received: July 31, 2015; Revised: April 5, 2016; Accepted: June 16, 2016; Published: July 14, 2016. We thank Juliane Winkler for sharing plasmids and MC4100 strain and Eric J. Stewart for sharing data. We furthermore thank Kim Sneppen, Namiko Mitarai, Kenn Gerdes, and Anne Grapin-Botton for their input. A.T., S.S., and H.N. were funded by the Danish National Research Foundation (C-MOL and StemPhys Centers). S.V. was funded by Niels Bohr International Academy Postdoctoral Fellowship. Author Contributions: A.T., S.V., and H.N. conceived and performed experiments, analyzed the data, and wrote manuscript. A.K. contributed to mathematical model and wrote the manuscript. S.S. contributed to the experiments and wrote the manuscript. A.T. secured funding.
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Danish National Research FoundationUNSPECIFIED
Niels Bohr International AcademyUNSPECIFIED
Issue or Number:2
Record Number:CaltechAUTHORS:20160725-123339637
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Official Citation:Søren Vedel, Harry Nunns, Andrej Košmrlj, Szabolcs Semsey, Ala Trusina, Asymmetric Damage Segregation Constitutes an Emergent Population-Level Stress Response, Cell Systems, Volume 3, Issue 2, 24 August 2016, Pages 187-198, ISSN 2405-4712, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:69197
Deposited By: Tony Diaz
Deposited On:25 Jul 2016 20:34
Last Modified:21 Apr 2020 18:19

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