Emergence of Supercoiling-Mediated Regulatory Networks through the Evolution of Bacterial Chromosome Organization

DNA supercoiling - the level of twisting and writhing of the DNA molecule around itself - plays a major role in the regulation of gene expression in bacteria by modulating promoter activity. The level of DNA supercoiling is a dynamic property of the chromosome, which varies both at local and global scales, in response to external factors such as environmental perturbations and to internal factors including gene transcription. As such, local variations in supercoiling could in theory couple the expression levels of neighboring genes by creating feedback loops between their transcription rates. However, the impact of such supercoiling-mediated interactions on the regulation of gene expression remains uncertain. In this work, we study how this coupling between transcription and supercoiling could shape genome organization and help regulate gene transcription. We present a model of genome evolution in which individuals whose gene transcription rates are coupled to supercoiling must adapt to two environments that induce different global supercoiling levels. In this model, we observe the evolution of whole-genome regulatory networks that provide control over gene expression by leveraging the transcription-supercoiling coupling, and show that the structure of these networks is underpinned by the organization of genes along the chromosome at several scales. Local variations in DNA supercoiling could therefore help jointly shape both gene regulation and genome organization during evolution.