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BMC Systems Biology

, 5:128

Empirical systems biology

Abstract

BackgroundHow transcriptionally regulated gene expression evolves under natural selection is an open question. The cost and benefit of gene expression are the driving factors. While the former can be determined by gratuitous induction, the latter is difficult to measure directly.

ResultsWe addressed this problem by decoupling the regulatory and metabolic function of the Escherichia coli lac system, using an inducer that cannot be metabolized and a carbon source that does not induce. Growth rate measurements directly identified the induced expression level that maximizes the metabolism benefits minus the protein production costs, without relying on models. Using these results, we established a controlled mismatch between sensing and metabolism, resulting in sub-optimal transcriptional regulation with the potential to improve by evolution. Next, we tested the evolutionary response by serial transfer. Constant environments showed cells evolving to the predicted expression optimum. Phenotypes with decreased expression emerged several hundred generations later than phenotypes with increased expression, indicating a higher genetic accessibility of the latter. Environments alternating between low and high expression demands resulted in overall rather than differential changes in expression, which is explained by the concave shape of the cross-environmental tradeoff curve that limits the selective advantage of altering the regulatory response.

ConclusionsThis work indicates that the decoupling of regulatory and metabolic functions allows one to directly measure the costs and benefits that underlie the natural selection of gene regulation. Regulated gene expression is shown to evolve within several hundreds of generations to optima that are predicted by these costs and benefits. The results provide a step towards a quantitative understanding of the adaptive origins of regulatory systems.

Electronic supplementary materialThe online version of this article doi:10.1186-1752-0509-5-128 contains supplementary material, which is available to authorized users.

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Author: Frank J Poelwijk - Philip D Heyning - Marjon GJ de Vos - Daniel J Kiviet - Sander J Tans

Source: https://link.springer.com/







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