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Bioinformatics Advance Access published online on July 9, 2004
Bioinformatics, doi:10.1093/bioinformatics/bth393
Bioinformatics © Oxford University Press 2004; all rights reserved
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Received November 11, 2003
Revised June 3, 2004
Accepted July 2, 2004

Article

DNA structure constraint is probably a fundamental factor inducing CpG deficiency in bacteria

Yong Wang 1* Frederick C. C. Leung 1

1 Department of Zoology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

* To whom correspondence should be addressed. E-mail: wangyong{at}hkucc.hku.hk.


  Abstract

Motivation: It has been speculated that CpG dinucleotide deficiency in genomes is a consequence of DNA methylation. However, this hypothesis does not adequately explain CpG deficiency in bacteria. The hypothesis based on DNA structure constraint as an alternative explanation was therefore examined.

Results: By comparing real bacterial genomes and Markov artificial genomes in the second order, we found that the core structure of a restricted pattern, the TTCGAA pattern, was under-represented in low GC content bacterial genomes regardless of CpG dinucleotide level. This is in contrast to the AACGTT pattern, indicating that the counter-selection is context-dependent. Further study discovered 9 under-represented patterns that were supposed able to induce DNA structure constraint. In summary, most of them are in TTCGNA and TTCGAN patterns in both DNA strands. An explanation is also proposed for the strong correlation between GC content and CpG deficiency. The result of random sequence simulation showed that the occurrences of these patterns were correlated with GC content, as well as the percentage of CpG dinucleotides being trapped in these patterns. Finally, we suggest that the degree of counter-selection against these restricted patterns could be influenced by global GC content of a genome.


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