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Universal patterns of purifying selection at noncoding positions in bacteria.

Nacho Molina¹, Erik van Nimwegen

¹Biozentrum, the University of Basel, and Swiss Institute of Bioinformatics, 4056-CH, Basel, Switzerland.

Genome Research

|November 23, 2007

Summary

Bacterial genomes maintain a consistent number of regulatory sites per intergenic region regardless of size. This is achieved by adjusting the number of transcription factors (TFs) and their target sites, optimizing gene regulation across diverse genome sizes.

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Area of Science:

Genomics
Bioinformatics
Evolutionary Biology

Background:

Regulatory elements are crucial for gene expression control.
Understanding how regulatory site density varies with genome size is key to deciphering genome evolution.
Previous studies have not fully explored the relationship between bacterial genome size and regulatory site distribution.

Purpose of the Study:

To investigate the relationship between genome size and the number of regulatory sites per intergenic region in bacteria.
To identify universal patterns of selection acting on noncoding DNA.
To characterize the structural changes in transcription regulatory networks across different bacterial genome sizes.

Main Methods:

Developed a novel method for detecting purifying selection at noncoding positions in bacterial genomes.
Quantified evidence of purifying selection across noncoding regions in bacterial clades.
Analyzed sequence diversity of conserved DNA words in intergenic regions.

Main Results:

Identified universal positional profiles of selection near gene start and end sites, consistent with transcriptional regulation.
Found strong evidence for selection optimizing translation initiation efficiency, including specific sequence compositions and RNA secondary structure avoidance.
Despite a quadratic increase in transcription factors (TFs) with genome size, the average number of regulatory sites per intergenic region remained constant.
Demonstrated that small genomes utilize fewer TFs with more target sites, while large genomes employ more TFs with fewer individual target sites.

Conclusions:

Bacterial genomes exhibit conserved regulatory site density across varying genome sizes.
Genome size influences the architecture of transcription regulatory networks, shifting from a 'few regulators, many targets' model in small genomes to a 'many regulators, few targets' model in large genomes.
Selection plays a significant role in shaping noncoding DNA composition and regulatory element organization in bacteria.