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Emergence of Supercoiling-Mediated Regulatory Networks through the Evolution of Bacterial Chromosome Organizationuse asterix (*) to get italics
Théotime Grohens, Sam Meyer, Guillaume BeslonPlease use the format "First name initials family name" as in "Marie S. Curie, Niels H. D. Bohr, Albert Einstein, John R. R. Tolkien, Donna T. Strickland"
<p>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 still 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 local 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.</p>, should fill this box only if you chose 'All or part of the results presented in this preprint are based on data'. URL must start with http:// or https:// should fill this box only if you chose 'Scripts were used to obtain or analyze the results'. URL must start with http:// or https://;origin= should fill this box only if you chose 'Codes have been used in this study'. URL must start with http:// or https://
DNA supercoiling, gene transcription, evolution, genome organization
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Biophysics, Evolutionary Biology, Systems biology
Patrick Sobezko (, Sarah Harris (, Amandine Veber suggested: Philippe Robert, Ivan Junier suggested: In this revised version of their preprint, the authors have done an excellent job of introducing their model and the biology related to DNA supercoiling more effectively., Ivan Junier suggested: Altogether, this work provides an insightful theoretical analysis of the potential impact of the coupling between DNA supercoiling and transcription on the evolution of genome organization and on the role of DNA supercoiling in regulatory networks. For these reasons, I strongly recommend the publication of this manuscript., Ivan Junier suggested: In the following, I provide additional comments that the authors could consider for the final version of their manuscript., Ivan Junier suggested: - I believe there is still room to improve the evolutionary take-home message: i) by mentioning in the title the term "adaptation" or "evolution", and ii) by rephrasing, for example, in the abstract the sentence "We present a model of gene transcription and DNA supercoiling..." to something like "We present a model of genome evolution driven by transcription-supercoiling coupling...". This is particularly important given that the work is (nicely) introduced by stating "Here, we address a different question that has never been subject to detailed analysis: how the transcription-supercoiling coupling may drive genome evolution." (Lines 141-143) and concluded with "To the best of our knowledge, this work is the first to propose a model to investigate the role of the coupling between gene transcription and DNA supercoiling in the evolution of the structure of bacterial genomes." (Lines 596-598), Ivan Junier suggested: - In response to their response to my point A.2: I do not think that anyone can argue for a specific value for dmax that is more relevant than another one, as we do not have a good understanding of the situation in vivo. In particular, strong heterogeneities along the genome are expected. Instead, I believe the authors' statement that "values of dmax under 4 kb actually prevent the evolution of inhibition of A genes in environment B (data not shown)" deserves to be mentioned in the manuscript as i) it helps to understand the authors' choice of dmax=5 kb and ii) this is an interesting prediction of the model., Ivan Junier suggested: - In response to their response to my point A.3: I agree with the authors' response that $\delta \sigma = 0$ is not compatible with two environments. However, I wonder whether the high sensitivity of the system to the introduction of $\delta \sigma \neq 0$ does not obscure the existence of two solutions at $\delta \sigma = 0$. This could be easily tested. No need for them to be recommenders of PCI Math Comp Biol. Please do not suggest reviewers for whom there might be a conflict of interest. Reviewers are not allowed to review preprints written by close colleagues (with whom they have published in the last four years, with whom they have received joint funding in the last four years, or with whom they are currently writing a manuscript, or submitting a grant proposal), or by family members, friends, or anyone for whom bias might affect the nature of the review - see the code of conduct
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2023-06-30 10:34:28
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