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This article is part of the supplement: Ninth International Conference on Bioinformatics (InCoB2010): Bioinformatics

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Gradual transition from mosaic to global DNA methylation patterns during deuterostome evolution

Kohji Okamura12, Kazuaki A Matsumoto13 and Kenta Nakai14*

Author Affiliations

1 Human Genome Centre, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato Ward, Tokyo 108-8639, Japan

2 Centre for Informational Biology, Ochanomizu University, 2-1-1 Otsuka, Bunkyo Ward, Tokyo 112-8610, Japan

3 Department of Electric Engineering and Bioscience, Graduate School of Sciences and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku Ward, Tokyo 162-8480, Japan

4 Institute for Bioinformatics Research and Development, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi 332-0012, Japan

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BMC Bioinformatics 2010, 11(Suppl 7):S2  doi:10.1186/1471-2105-11-S7-S2

Published: 15 October 2010



DNA methylation by the Dnmt family occurs in vertebrates and invertebrates, including ascidians, and is thought to play important roles in gene regulation and genome stability, especially in vertebrates. However, the global methylation patterns of vertebrates and invertebrates are distinctive. Whereas almost all CpG sites are methylated in vertebrates, with the exception of those in CpG islands, the ascidian genome contains approximately equal amounts of methylated and unmethylated regions. Curiously, methylation status can be reliably estimated from the local frequency of CpG dinucleotides in the ascidian genome. Methylated and unmethylated regions tend to have few and many CpG sites, respectively, consistent with our knowledge of the methylation status of CpG islands and other regions in mammals. However, DNA methylation patterns and levels in vertebrates and invertebrates have not been analyzed in the same way.


Using a new computational methodology based on the decomposition of the bimodal distributions of methylated and unmethylated regions, we estimated the extent of the global methylation patterns in a wide range of animals. We then examined the epigenetic changes in silico along the phylogenetic tree. We observed a gradual transition from fractional to global patterns of methylation in deuterostomes, rather than a clear demarcation between vertebrates and invertebrates. When we applied this methodology to six piscine genomes, some of which showed features similar to those of invertebrates.


The mammalian global DNA methylation pattern was probably not acquired at an early stage of vertebrate evolution, but gradually expanded from that of a more ancient organism.