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  Evolutionary consequences of DNA methylation on the GC content in vertebrate genomes

Mugal, C. F., Arndt, P. F., Holm, L., & Ellegren, H. (2015). Evolutionary consequences of DNA methylation on the GC content in vertebrate genomes. G3: Genes, Genomes, Genetics, 5(3), 441-447. doi:10.1534/g3.114.015545.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-3A73-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-3A74-6
Genre: Journal Article

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 Creators:
Mugal, Carina F.1, Author
Arndt, Peter F.2, Author              
Holm, Lena3, Author
Ellegren, Hans1, Author
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1Department of Ecology and Genetics, Uppsala University, SE-752 36 Uppsala, Sweden, ou_persistent22              
2Evolutionary Genomics (Peter Arndt), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479638              
3Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, SE-756 51 Uppsala, Sweden , ou_persistent22              

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Free keywords: Animals Base Composition Chickens DNA Methylation Evolution, Molecular Genome, Human Humans CpG hypermutability DNA methylation GC content GC isochores GC-biased gene conversion
 Abstract: The genomes of many vertebrates show a characteristic variation in GC content. To explain its origin and evolution, mainly three mechanisms have been proposed: selection for GC content, mutation bias, and GC-biased gene conversion. At present, the mechanism of GC-biased gene conversion, i.e., short-scale, unidirectional exchanges between homologous chromosomes in the neighborhood of recombination-initiating double-strand breaks in favor for GC nucleotides, is the most widely accepted hypothesis. We here suggest that DNA methylation also plays an important role in the evolution of GC content in vertebrate genomes. To test this hypothesis, we investigated one mammalian (human) and one avian (chicken) genome. We used bisulfite sequencing to generate a whole-genome methylation map of chicken sperm and made use of a publicly available whole-genome methylation map of human sperm. Inclusion of these methylation maps into a model of GC content evolution provided significant support for the impact of DNA methylation on the local equilibrium GC content. Moreover, two different estimates of equilibrium GC content, one that neglects and one that incorporates the impact of DNA methylation and the concomitant CpG hypermutability, give estimates that differ by approximately 15% in both genomes, arguing for a strong impact of DNA methylation on the evolution of GC content. Thus, our results put forward that previous estimates of equilibrium GC content, which neglect the hypermutability of CpG dinucleotides, need to be reevaluated.

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Language(s): eng - English
 Dates: 2015-01-15
 Publication Status: Published online
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 Identifiers: DOI: 10.1534/g3.114.015545
ISSN: 2160-1836 (Electronic)
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Title: G3: Genes, Genomes, Genetics
Source Genre: Journal
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Publ. Info: Genetics Society of America
Pages: - Volume / Issue: 5 (3) Sequence Number: - Start / End Page: 441 - 447 Identifier: -