Paper on genome-wide structural variations impacting xenogene silencing
In a paper, just published in Nucleic Acids Research, we use laboratory evolution and genome sequencing to show that a large duplication of ~40% of the chromosome, centred around the origin or replication and comprising many highly expressed genes, can compensate for the global gene expression imbalance caused by a perturbation of gene silencing operating on horizontally-acquired genes in the bacterium E. coli. The experimental work was performed by Raji Srinivasan, supported by Vittore Scolari (now Dr. Vittore Scolari). This work is part of a wide-ranging collaboration we have with the Genomic Physics Group, lead by Marco Cosentino Lagomarsino at UPMC, Paris.
The abstract of the paper reads as follows:
The gene expression state of exponentially growing Escherichia coli cells is manifested by high expression of essential and growth-associated genes and low levels of stress-related and horizontally acquired genes. An important player in maintaining this homeostasis is the H-NS-StpA gene silencing system. A Δhns-stpA deletion mutant results in high expression of otherwise-silent horizontally acquired genes, many located in the terminus-half of the chromosome, and an indirect downregulation of many highly expressed genes. The Δhns-stpA double mutant displays slow growth. Using laboratory evolution we address the evolutionary strategies that E. coli would adopt to redress this gene expression imbalance. We show that two global gene regulatory mutations—(i) point mutations inactivating the stress-responsive sigma factor RpoS or σ38 and (ii) an amplification of ∼40% of the chromosome centred around the origin of replication—converge in partially reversing the global gene expression imbalance caused by Δhns-stpA. Transcriptome data of these mutants further show a three-way link amongst the global gene regulatory networks of H-NS and σ38, as well as chromosome architecture. Increasing gene expression around the terminus of replication results in a decrease in the expression of genes around the origin and vice versa; this appears to be a persistent phenomenon observed as an association across ∼300 publicly-available gene expression data sets for E. coli. These global suppressor effects are transient and rapidly give way to more specific mutations, whose roles in reversing the growth defect of H-NS mutations remain to be understood.