Statistical analysis of the spatial distribution of operons in the transcriptional regulation network of Escherichia coli

We have performed a statistical analysis of the spatial distribution of operons along the DNA in the transcriptional regulation network of Escherichia coli. The analysis reveals that pairs of operons that regulate each other and those that are co-regulated tend to lie much closer to one another than would be expected for a random network. Moreover, these pairs of operons tend to be transcribed in diverging directions. This spatial arrangement of operons allows the upstream regulatory domains to overlap and interfere with each other and our analysis also demonstrates the statistical significance of this motif of overlapping operons. Overlapping operons afford additional regulatory control, such as the correlated or anticorrelated expression of operons. We show by a mean-field analysis of a feed-forward loop that overlapping operons can drastically enhance the performance of gene regulatory networks. Our results suggest that regulatory control can provide a selective pressure that drives operons together in the course of evolution. (C) 2004 Elsevier Ltd. All rights reserved.