The Parameter-Fitness Landscape of lexA Autoregulation in Escherichia coli

Abstract

Feedback mechanisms are critical to control physiological responses. In gene regulation, one important example, termed negative autoregulation (NAR), occurs when a transcription factor (TF) inhibits its own production. NAR is common across the tree of life, enabling rapid homeostatic control of gene expression. NAR behavior can be described in accordance with its core biochemical parameters, but how constrained these parameters are by evolution is unclear. Here, we describe a model genetic network controlled by an NAR circuit within the bacterium Escherichia coli and elucidate these constraints by experimentally changing a key parameter and measuring its effect on circuit response and fitness. This analysis yielded a parameter-fitness landscape representing the genetic network, providing a window into what gene-environment conditions favor evolution of this regulatory strategy.