Abstract
The evolutionary processes operating in the DNA regions that participate in the regulation of gene expression are poorly understood. In Escherichia coli, we have established a sequence pattern that distinguishes regulatory from nonregulatory regions. The density of promoter-like sequences, that could be recognizable by RNA polymerase and may function as potential promoters, is high within regulatory regions, in contrast to coding regions and regions located between convergently transcribed genes. Moreover, functional promoter sites identified experimentally are often found in the subregions of highest density of promoter-like signals, even when individual sites with higher binding affinity for RNA polymerase exist elsewhere within the regulatory region. In order to see the generality of this pattern, we have analyzed 43 additional genomes belonging to most established bacterial phyla. Differential densities between regulatory and nonregulatory regions are detectable in most of the analyzed genomes, with the exception of those that have evolved toward extreme genome reduction. Thus, presence of this pattern follows that of genes and other genomic features that require weak selection to be effective in order to persist. On this basis, we suggest that the loss of differential densities in the reduced genomes of host-restricted pathogens and symbionts is an outcome of the process of genome degradation resulting from the decreased efficiency of purifying selection in highly structured small populations. This implies that the differential distribution of promoter-like signals between regulatory and nonregulatory regions detected in large bacterial genomes confers a significant, although small, fitness advantage. This study paves the way for further identification of the specific types of selective constraints that affect the organization of regulatory regions and the overall distribution of promoter-like signals through more detailed comparative analyses among closely related bacterial genomes.
Highlights
For both prokaryotes and eukaryotes, understanding of the organizational structure and mode of evolution of regulatory DNA sequences is incomplete
In Escherichia coli, RNA polymerase (RNAP) is composed of a core complex of a, b, b9, and x subunits and one of a variety of r factors, the primary one being r70, which is essential for general transcription in exponentially growing cells
We argue that the phylogenetic distribution of this differential density pattern implies that this genomic feature is maintained by weak natural selection, and we discuss possible functional roles for the high redundancy of promoter-like signals in the regulatory regions of large bacterial genomes
Summary
For both prokaryotes and eukaryotes, understanding of the organizational structure and mode of evolution of regulatory DNA sequences is incomplete. It has been recently shown that most of the regulatory regions in E. coli do not contain a single promoter sequence [1] but rather display high densities of potential RNAP-r70 binding sites, forming clusters of overlapping promoter-like signals. It has been shown that natural selection acts to remove spurious occurrences of the two consensus words of the r70 promoter (TTGACA and TATAAT) from both coding and noncoding regions in several eubacterial genomes, implying that it is disadvantageous to maintain misplaced sites which can strongly bind RNAP-r70 and interfere with proper gene expression [7] This suggests that the observed excess of promoter-like signals in regulatory regions is likely to be the result of natural selection for some past or present function.
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