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Theory Biosci. 2013 Mar;132(1):47-60. doi: 10.1007/s12064-012-0167-y. Epub 2012 Nov 7.

The correlation of genome size and DNA methylation rate in metazoans.

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Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, 35037, Marburg, Germany.


Total DNA methylation rates are well known to vary widely between different metazoans. The phylogenetic distribution of this variation, however, has not been investigated systematically. We combine here publicly available data on methylcytosine content with the analysis of nucleotide compositions of genomes and transcriptomes of 78 metazoan species to trace the evolution of abundance and distribution of DNA methylation. The depletion of CpG and the associated enrichment of TpG and CpA dinucleotides are used to infer the intensity and localization of germline CpG methylation and to estimate its evolutionary dynamics. We observe a positive correlation of the relative methylation of CpG motifs with genome size. We tested this trend successfully by measuring total DNA methylation with LC/MS in orthopteran insects with very different genome sizes: house crickets, migratory locusts and meadow grasshoppers. We hypothesize that the observed correlation between methylation rate and genome size is due to a dependence of both variables from long-term effective population size and is driven by the accumulation of repetitive sequences that are typically methylated during periods of small population sizes. This process may result in generally methylated, large genomes such as those of jawed vertebrates. In this case, the emergence of a novel demethylation pathway and of novel reader proteins for methylcytosine may have enabled the usage of cytosine methylation for promoter-based gene regulation. On the other hand, persistently large populations may lead to a compression of the genome and to the loss of the DNA methylation machinery, as observed, e.g., in nematodes.

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