The adaptive landscapes of three global Escherichia coli transcriptional regulators

Abstract

The evolution of new gene regulation is an important source of evolutionary adaptations and innovations, especially when organisms encounter new environments. At its heart is the process by which new and strong DNA binding sites of transcription factors (TFs) originate in evolution. Here we study the potential of Darwinian evolution to create strong binding sites for the three Escherichia coli global transcription factors CRP, Fis, and IHF. Using a massively parallel reporter assay, we measure for each TF the ability of more than 30,000 binding sites to regulate gene expression. We use the resulting data to map the adaptive landscape of each TF. We find that all three landscapes are rugged, epistatic, and harbor multiple peaks. The highest peaks are widely scattered throughout the landscape, indicating that strong regulation can be achieved by very different binding sites. Landscape ruggedness does not prevent the evolution of strong regulation, because more than 10% of evolving populations can attain one of the highest peaks. Adaptive evolution starting from the same DNA sequence can attain more than one high peak, and some high peaks are more likely to be reached than others. Our experiments show that de novo adaptive evolution of new gene regulation is feasible. It is also subject to a blend of chance, historical contingency, and evolutionary biases that favor some peaks and evolutionary paths over others.

Competing Interest Statement

The authors have declared no competing interest.