Evolutionary Pushes, Gene Expression Homeostasis and Chromosome Architecture in Bacteria.

Abstract : Bacterial chromosomes are structured in as yet poorly understood ways, but has been attracting significant interest of late. It may be that there are many possible topologies but comparative genomic analysis of translocations suggest these topologies are not phylogenetically constrained, and therefore opening a debate on their selective value. But what is not to be debated is what I would term the "sanctity of the Ori-Ter axis", or the replication-dependent gene organisation of the chromosome. Circular bacterial chromosomes have a single origin or replication (Ori) - replication proceeds bidirectionally at the same rate on either side of the Ori, down the Ori-Ter axis - terminating at the diametrically opposite Ter (terminus of replication). For many bacteria - more starkly for fast-growing bacteria - the copy number of the genetic material around the Ori is generally much higher than that around the Ter, as a result of of replication accounting for much of the bug's life time. I will show evidence from comparative genomics that various aspects of gene organisation may be selected by growth rate. Specifically, I will build on evidence that transcriptionally silent horizontally-acquired genes - a major aspect of bacterial evolution - are more likely to be encoded around the terminus, by showing the following, using experimental genomics in the model bacterium Escherichia coli: (a) perturbation of gene silencing results in an global transcriptional imbalance - encompassing direct effects of the perturbation and the collateral damage - targeting the Ori- and the Ter-half of the chromosome in opposite ways; (b) E. coli can adapt to such an imbalance by duplicating as much as 40% of its chromosome around the Ori, resulting in a partial reversal of the transcriptional state arising from the perturbation of gene silencing; (c) the antagonistic transcriptional profiles of the Ori and the Ter halves of the chromosome may be a persistent phenomenon spread across many growth conditions. These indicate the presence of a large, genome-wide pattern of gene expression homeostasis that is linked to the replication-dependent organisation of the chromosome, and that this can be perturbed by de-silencing horizontally-acquired genes.