TY - JOUR
T1 - Robustness and evolvability of heterogeneous cell populations
AU - Kucharavy, Andrei
AU - Rubinstein, Boris
AU - Zhu, Jin
AU - Li, Rong
N1 - Funding Information:
We thank O. Tenaillon, S. Matuszewski, G. Fischer, J.E. Gern, R. Yu, D. Dahlen, A. Baryshnikova, and D. Georgess for insightful discussions and O. Tenaillon, H.-J. Tsai, S. Matuszewski, and G. Fischer for comments on the manuscript. This work was supported by Grant R35 GM118172 from the National Institutes of Health to R.L. Any custom software used in this publication and data sets used to obtain the results in this manuscript are listed in Materials and Methods and are in open access in the indicated GitHub repositories.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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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U2 - 10.1091/mbc.E18-01-0070
DO - 10.1091/mbc.E18-01-0070
M3 - Article
C2 - 29851566
AN - SCOPUS:85048178772
VL - 29
SP - 1400
EP - 1409
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 11
ER -