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Biology subjects

Gemo, P.

Publications and source records attributed to Gemo, P..

2 recordsLinked to original sources

On the interactions of DNA replication and transcriptional regulation

DNA replication introduces a gradient of gene copy numbers, and in Bacteria it affects gene expression accordingly. In E. coli and other species, the slope of the gradient averaged over the population can be predicted on the basis of its relationship with growth rate. In this work we integrated this growth- and position-dependent gradient into a classical transcriptional regulation model, to highlight their interaction. The theoretical treatment of our model highlights that the sensitivity to transcription factor-mediated regulations acquires an additional dimension related to the position of a locus on the oriter axis and to division time. This reinforces the idea of replication as an additional layer in gene regulation. We highlight here that replication- and transcription factor-mediated regulations can in theory work in concert or counteract each other, and we discuss why this is important from an evolutionary point of view with respect to both steady state transcript abundance and its variance across conditions. Finally, we note that this treatment may improve the estimation of kinetic parameters for transcription factor activity using RNA-seq data, and the estimation of the dispersion factor in differential gene expression analysis when division time across conditions changes significantly.

systems biology↗

The selective force driving metabolic operon assembly

The evolution of operons has puzzled evolutionary biologists since their discovery and many theories exist to explain their emergence and spreading. The presence of several plausible hypotheses dealing with operon emergence/evolution/spreading is indicative of the absence of a universal causal factor for this evolutionary process. Here, we argue that the way in which DNA replication and cell division are coupled in microbial species introduces an additional selective force that may be responsible for the clustering of functionally related genes on chromosomes. We interpret this as a preliminary and necessary step in operon formation. Specifically, we start from the observation that during DNA replication differences in copy number of genes that are found at distant loci on the same chromosome arm exist. We provide theoretical considerations suggesting that, when genes of the same metabolic process are far away on the chromosome, this results in perturbations to metabolic homeostasis. By formalizing the effect of DNA replication on metabolic homeostasis based on Metabolic Control Analysis, we show that the above situation provides a selective force that can drive the formation of gene clusters and operons. Finally, we confirmed that, in present-day genomes, this force is significantly stronger in those species where the average number of active replication forks is larger and quantify the theoretical contribution of this feature on the distribution of extant gene clusters and operons.

systems biology↗