Emergence of Supercoiling-Mediated Regulatory Networks through 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 the global scale in response to external factors such as environmental perturbations, and at the local scale in response to internal factors including gene transcription itself. These local variations can couple the transcription rates of neighboring genes by creating feedback loops. The importance of the role of such supercoiling-mediated interactions in the regulation of gene expression however remains uncertain. In this work, we study how this coupling could play a part in the bacterial regulatory landscape by coevolving with genome organization. We present a model of gene transcription and DNA supercoiling at the whole-genome scale, in which individuals must evolve gene expression levels adapted to two different environments. In this model, we observe the evolution of whole-genome regulatory networks that provide fine 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 jointly help shape both gene regulation and genome organization during evolution. ### Competing Interest Statement The authors have declared no competing interest.