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Robustness and evolvability of heterogeneous cell populations

Biological systems are endowed with two fundamental but seemingly contradictory properties: robustness, the ability to withstand environmental fluctuations and genetic variability; and evolvability, the ability to acquire selectable and heritable phenotypic changes. Cell populations with heterogeneo...

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Detalles Bibliográficos
Autores principales: Kucharavy, Andrei, Rubinstein, Boris, Zhu, Jin, Li, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994894/
https://www.ncbi.nlm.nih.gov/pubmed/29851566
http://dx.doi.org/10.1091/mbc.E18-01-0070
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author Kucharavy, Andrei
Rubinstein, Boris
Zhu, Jin
Li, Rong
author_facet Kucharavy, Andrei
Rubinstein, Boris
Zhu, Jin
Li, Rong
author_sort Kucharavy, Andrei
collection PubMed
description Biological systems are endowed with two fundamental but seemingly contradictory properties: robustness, the ability to withstand environmental fluctuations and genetic variability; and evolvability, the ability to acquire selectable and heritable phenotypic changes. Cell populations with heterogeneous genetic makeup, such as those of infectious microbial organisms or cancer, rely on their inherent robustness to maintain viability and fitness, but when encountering environmental insults, such as drug treatment, these populations are also poised for rapid adaptation through evolutionary selection. In this study, we develop a general mathematical model that allows us to explain and quantify this fundamental relationship between robustness and evolvability of heterogeneous cell populations. Our model predicts that robustness is, in fact, essential for evolvability, especially for more adverse environments, a trend we observe in aneuploid budding yeast and breast cancer cells. Robustness also compensates for the negative impact of the systems’ complexity on their evolvability. Our model also provides a mathematical means to estimate the number of independent processes underlying a system’s performance and identify the most generally adapted subpopulation, which may resemble the multi-drug-resistant “persister” cells observed in cancer.
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spelling pubmed-59948942018-08-16 Robustness and evolvability of heterogeneous cell populations Kucharavy, Andrei Rubinstein, Boris Zhu, Jin Li, Rong Mol Biol Cell Articles Biological systems are endowed with two fundamental but seemingly contradictory properties: robustness, the ability to withstand environmental fluctuations and genetic variability; and evolvability, the ability to acquire selectable and heritable phenotypic changes. Cell populations with heterogeneous genetic makeup, such as those of infectious microbial organisms or cancer, rely on their inherent robustness to maintain viability and fitness, but when encountering environmental insults, such as drug treatment, these populations are also poised for rapid adaptation through evolutionary selection. In this study, we develop a general mathematical model that allows us to explain and quantify this fundamental relationship between robustness and evolvability of heterogeneous cell populations. Our model predicts that robustness is, in fact, essential for evolvability, especially for more adverse environments, a trend we observe in aneuploid budding yeast and breast cancer cells. Robustness also compensates for the negative impact of the systems’ complexity on their evolvability. Our model also provides a mathematical means to estimate the number of independent processes underlying a system’s performance and identify the most generally adapted subpopulation, which may resemble the multi-drug-resistant “persister” cells observed in cancer. The American Society for Cell Biology 2018-06-01 /pmc/articles/PMC5994894/ /pubmed/29851566 http://dx.doi.org/10.1091/mbc.E18-01-0070 Text en © 2018 Kucharavy et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0/ This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Kucharavy, Andrei
Rubinstein, Boris
Zhu, Jin
Li, Rong
Robustness and evolvability of heterogeneous cell populations
title Robustness and evolvability of heterogeneous cell populations
title_full Robustness and evolvability of heterogeneous cell populations
title_fullStr Robustness and evolvability of heterogeneous cell populations
title_full_unstemmed Robustness and evolvability of heterogeneous cell populations
title_short Robustness and evolvability of heterogeneous cell populations
title_sort robustness and evolvability of heterogeneous cell populations
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994894/
https://www.ncbi.nlm.nih.gov/pubmed/29851566
http://dx.doi.org/10.1091/mbc.E18-01-0070
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