Primate CpG Islands Are Maintained by Heterogeneous Evolutionary Regimes Involving Minimal Selection

被引:107
作者
Cohen, Netta Mendelson [1 ]
Kenigsberg, Ephraim [1 ]
Tanay, Amos [1 ]
机构
[1] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel
关键词
BIASED GENE CONVERSION; DIFFERENTIALLY METHYLATED REGIONS; PLURIPOTENT STEM-CELLS; DNA METHYLATION; HUMAN GENOME; BINDING SITES; HYPERMETHYLATION; PATTERNS; FREQUENCIES; SEQUENCES;
D O I
10.1016/j.cell.2011.04.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mammalian CpG islands are key epigenomic elements that were first characterized experimentally as genomic fractions with low levels of DNA methylation. Currently, CpG islands are defined based on their genomic sequences alone. Here, we develop evolutionary models to show that several distinct evolutionary processes generate and maintain CpG islands. One central evolutionary regime resulting in enriched CpG content is driven by low levels of DNA methylation and consequentially low rates of CpG deamination. Another major force forming CpG islands is biased gene conversion that stabilizes constitutively methylated CpG islands by balancing rapid deamination with CpG fixation. Importantly, evolutionary analysis and population genetics data suggest that selection for high CpG content is not a significant factor contributing to conservation of CpGs in differentially methylated regions. The heterogeneous, but not selective, origins of CpG islands have direct implications for the understanding of DNA methylation patterns in healthy and diseased cells.
引用
收藏
页码:773 / 786
页数:14
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