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

Okamura K, Matsumoto KA, Nakai K - BMC Bioinformatics (2010)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

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Histograms showing the CpG-score frequencies in 2-kb genomic fragments. Each histogram covers the whole genome of the (A) sea urchin, (B) lancelet (amphioxus), (C) ascidian, (D) zebrafish, (E) frog, (F) anole (a kind of lizard), (G) chicken, (H) platypus, (I) opossum, (J) dog, (K) mouse, or (L) human. Apparent bimodal distributions are seen in the invertebrate deuterostomes. All distributions were compulsorily separated into two normal distributions. The two decomposed Gaussian curves and a merged curve are also drawn on each histogram.
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Figure 3: Histograms showing the CpG-score frequencies in 2-kb genomic fragments. Each histogram covers the whole genome of the (A) sea urchin, (B) lancelet (amphioxus), (C) ascidian, (D) zebrafish, (E) frog, (F) anole (a kind of lizard), (G) chicken, (H) platypus, (I) opossum, (J) dog, (K) mouse, or (L) human. Apparent bimodal distributions are seen in the invertebrate deuterostomes. All distributions were compulsorily separated into two normal distributions. The two decomposed Gaussian curves and a merged curve are also drawn on each histogram.

Mentions: Among the deuterostomes, we chose the genomes of Strongylocentrotus purpuratus (purple sea urchin), Branchiostoma floridae (Florida lancelet), Ciona intestinalis (ascidian), Danio rerio (zebrafish), Xenopus tropicalis (western clawed frog), Anolis carolinensis (green anole), Gallus gallus (chicken), Ornithorhynchus anatinus (platypus), Monodelphis domestica (gray short-tailed opossum), Canis familiaris (dog), Mus musculus (mouse), and Homo sapiens (human) to represent various clades, namely, echinoderms, cephalochordates, urochordates, fishes, amphibians, reptiles, avians, monotremes, marsupials, carnivores, rodents, and primates (Figure 2). We then examined the genome-wide distributions of the CpG scores for each of them, with a sliding window of 2 kb. In animals with a mosaic pattern, a bimodal distribution can be seen, arising from comparable amounts of low- and high-CpG-score regions. In other animals, only the low-CpG band is conspicuous, reflecting a global methylation pattern (Figure 3).


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

Okamura K, Matsumoto KA, Nakai K - BMC Bioinformatics (2010)

Histograms showing the CpG-score frequencies in 2-kb genomic fragments. Each histogram covers the whole genome of the (A) sea urchin, (B) lancelet (amphioxus), (C) ascidian, (D) zebrafish, (E) frog, (F) anole (a kind of lizard), (G) chicken, (H) platypus, (I) opossum, (J) dog, (K) mouse, or (L) human. Apparent bimodal distributions are seen in the invertebrate deuterostomes. All distributions were compulsorily separated into two normal distributions. The two decomposed Gaussian curves and a merged curve are also drawn on each histogram.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957685&req=5

Figure 3: Histograms showing the CpG-score frequencies in 2-kb genomic fragments. Each histogram covers the whole genome of the (A) sea urchin, (B) lancelet (amphioxus), (C) ascidian, (D) zebrafish, (E) frog, (F) anole (a kind of lizard), (G) chicken, (H) platypus, (I) opossum, (J) dog, (K) mouse, or (L) human. Apparent bimodal distributions are seen in the invertebrate deuterostomes. All distributions were compulsorily separated into two normal distributions. The two decomposed Gaussian curves and a merged curve are also drawn on each histogram.
Mentions: Among the deuterostomes, we chose the genomes of Strongylocentrotus purpuratus (purple sea urchin), Branchiostoma floridae (Florida lancelet), Ciona intestinalis (ascidian), Danio rerio (zebrafish), Xenopus tropicalis (western clawed frog), Anolis carolinensis (green anole), Gallus gallus (chicken), Ornithorhynchus anatinus (platypus), Monodelphis domestica (gray short-tailed opossum), Canis familiaris (dog), Mus musculus (mouse), and Homo sapiens (human) to represent various clades, namely, echinoderms, cephalochordates, urochordates, fishes, amphibians, reptiles, avians, monotremes, marsupials, carnivores, rodents, and primates (Figure 2). We then examined the genome-wide distributions of the CpG scores for each of them, with a sliding window of 2 kb. In animals with a mosaic pattern, a bimodal distribution can be seen, arising from comparable amounts of low- and high-CpG-score regions. In other animals, only the low-CpG band is conspicuous, reflecting a global methylation pattern (Figure 3).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

Show MeSH