DNA supercoiling, the under or overwinding of DNA, is known to strongly impact gene expression, as changes in levels of supercoiling directly influence transcription rates. In turn, gene transcription generates DNA supercoiling on each side of an advancing RNA polymerase. This coupling between DNA supercoiling and transcription may result in different outcomes, depending on neighboring gene orientations: divergent genes tend to increase transcription levels, convergent genes tend to inhibit each other, while tandem genes may exhibit more intricate relationships.

While several works have investigated the relationship between transcription and supercoiling, Grohens et al [1] address a different question: how does transcription-supercoiling coupling drive genome evolution? To this end, they consider a simple model of gene expression regulation where transcription level only depends on the local DNA supercoiling and where the transcription of one gene generates a linear profile of positive and negative DNA supercoiling on each side of it. They then make genomes evolve through genomic inversions only considering a fitness that reflects the ability of a genome to cope with two distinct environments for which different genes have to be activated or repressed.

Using this simple model, the authors illustrate how evolutionary adaptation via genomic inversions can adjust expression levels for enhanced fitness within specific environments, particularly with the emergence of relaxation-activated genes. Investigating the genomic organization of individual genomes revealed that genes are locally organized to leverage the transcription-supercoiling coupling for activation or inhibition, but larger-scale networks of genes are required to strongly inhibit genes (sometimes up to networks of 20 genes). Thus, supercoiling-mediated interactions between genes can implicate more than just local genes. Finally, they construct an "effective interaction graph" between genes by successively simulating gene knock-outs for all of the genes of an individual and observing the effect on the expression level of other genes. They observe a densely connected interaction network, implying that supercoiling-based regulation could evolve concurrently with genome organization in bacterial genomes.

References

[1] Théotime Grohens, Sam Meyer, Guillaume Beslon (2024) Emergence of Supercoiling-Mediated Regulatory Networks through the Evolution of Bacterial Chromosome Organization. bioRxiv, ver. 4 peer-reviewed and recommended by Peer Community in Mathematical and Computational Biology  https://doi.org/10.1101/2022.09.23.509185