Emergence of Supercoiling-Mediated Regulatory Networks through Bacterial Chromosome Rearrangements

DNA supercoiling, the level of twist and writhe 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 supercoiling is a dynamic property of the chromosome, and it changes in response to external and internal stimuli including many environmental perturbations but also, importantly, in response to gene transcription. As transcription itself depends on the level of supercoiling, the interplay between these two factors results in a coupling between the transcription rates, and expression levels, of neighboring genes. In this work, we study how the regulation of gene expression by the transcription-supercoiling coupling shapes the organization of bacterial genomes. We present an evolutionary model of gene transcription and DNA supercoiling at the whole-genome scale, in which individuals must adjust their gene expression levels to face different environments. We show that, in this model, whole-genome regulatory networks that provide fine control over gene expression evolve, and that these networks are grounded in the local organization of the genome in order to leverage the transcription-supercoiling coupling. Our results provide therefore important insight into the role of supercoiling in jointly shaping gene regulation and genome organization.