Abstract
In the transcriptional regulatory network (TRN) of a bacterium, the nodes are genes and a directed edge represents the action of a transcription factor (TF), encoded by the source gene, on the target gene. It is a condensed representation of a large number of biological observations and facts. Nonrandom features of the network are structural evidence of requirements for a reliable systemic function. For the bacterium Escherichia coli we here investigate the (Euclidean) distances covered by the edges in the TRN when its nodes are embedded in the real space of the circular chromosome. Our work is motivated by ’wiring economy’ research in Computational Neuroscience and starts from two contradictory hypotheses: (1) TFs are predominantly employed for long-distance regulation, while local regulation is exerted by chromosomal structure, locally coordinated by the action of structural proteins. Hence long distances should often occur. (2) A large distance between the regulator gene and its target requires a higher expression level of the regulator gene due to longer reaching times and ensuing increased degradation (proteolysis) of the TF and hence will be evolutionarily reduced. Our analysis supports the latter hypothesis.
Highlights
Approaches from Systems Biology have led to remarkable progress in understanding bacterial gene regulation[1,2,3]
Instrumental in this progress is the formal representation of gene regulation as a network of gene-gene interactions mediated by transcription factor (TF), which allowed identifying some design principles underlying this class of biological processes
Wiring economy and processing steps As a first step, we investigate, whether the spatial distances covered by the edges of the network and the average number of processing steps from source nodes to target nodes are larger or smaller than expected at random
Summary
Approaches from Systems Biology have led to remarkable progress in understanding bacterial gene regulation[1,2,3]. In particular accumulating evidence points to the need of considering the regulatory network as a spatially embedded structure, where the spatial organization of the circular bacterial chromosome contributes to the overall regulation of genes[9,10,11,12,13]. Genomic neighborhood and TRN explain gene expression patterns in a complementary fashion, suggesting a buffering mechanism between two types of regulation, one related to the TRN and the other to chromosomal structure[11] We here extend this line of investigation by studying the interplay of network features and spatial organization and their correlation with gene expression levels. Direct imaging of the E. coli chromosome shows a circular structure[18] that shades the view of a highly condensed nucleoid[19]
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