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Stressāresponse balance drives the evolution of a network module and its host genome
Gonzalez, Caleb Ray, J. Christian J. Manhart, Michael Adams, Ryhs M. Nevozhay, Dmitry Morozov, Alexandre V. Balazsi, Gabor
Gonzalez, Caleb
Ray, J. Christian J.
Manhart, Michael
Adams, Ryhs M.
Nevozhay, Dmitry
Morozov, Alexandre V.
Balazsi, Gabor
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Abstract
Stress response genes and their regulators form networks that underlie drug resistance. These networks often have an inherent tradeoff: their expression is costly in the absence of stress, but beneficial in stress. They can quickly emerge in the genomes of infectious microbes and cancer cells, protecting them from treatment. Yet, the evolution of stress resistance networks is not well understood. Here, we use a twoācomponent synthetic gene circuit integrated into the budding yeast genome to model experimentally the adaptation of a stress response module and its host genome in three different scenarios. In agreement with computational predictions, we find that: (i) intraāmodule mutations target and eliminate the module if it confers only cost without any benefit to the cell; (ii) intraā and extraāmodule mutations jointly activate the module if it is potentially beneficial and confers no cost; and (iii) a few specific mutations repeatedly fineātune the module's noisy response if it has excessive costs and/or insufficient benefits. Overall, these findings reveal how the timing and mechanisms of stress response network evolution depend on the environment.
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2015-08-01
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Wiley Open Access
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Gonzalez_2015_Wiley.pdf
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Drug Resistance, Experimental Evolution, Positive Feedback, Synthetic Gene Circuit, Tradeoff
Citation
Gonzalez, C., Ray, J. C. J., Manhart, M., Adams, R. M., Nevozhay, D., Morozov, A. V., & Balazsi, G. (2015). Stress-response balance drives the evolution of a network module and its host genome. Molecular Systems Biology, 11(8), 827ā827. doi:10.15252/msb.20156185