The Molecular Biophysics of Adaptation

Abstract

From molecular conformations to mass migrations, adaptation is a defining feature of life that is found across time and length scales. Here, we present a theory-experiment dialogue examining how adaptive behavior is manifested at the molecular level in the context of transcriptional regulation in bacteria. Using a statistical mechanical rendering of the Monod-Wyman-Changeux model of allostery, we draw parameter-free predictions of the level of gene expression from a regulated reporter as a function of an extracellular signal across a wide variety of strains. We then derive an expression for the free energy, enabling full data collapse of our experimental measurements onto a single master curve. With this arsenal of analytic ammunition, we then explore how physiological changes (rewiring carbon metabolism and varying temperature) and evolutionary perturbations (mutations with the regulatory protein) tune the level of gene expression and ultimately, the free energy of the system. We demonstrate that the adaptive response of the system can be mapped onto changes in the free energy, providing a set of diagnostic tools that identify which biophysical parameters are modified to yield the observed adaptation by examining the phenomenology of the data alone. These results illustrate that the free energy is the "natural variable" of the system and can be treated as a quantitative trait upon which evolutionary forces act, allowing for one to reduce the high-dimensional parameter space to a single-parameter description.

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