Evolutionary Dynamics of CpG islands

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 and analyzed based on their genomic sequences alone.  Here we develop novel 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.

Evolutionary Classification of CpG Islands 

The track shows contiguous (100bp or more) genomic elements with CpG content greater than 3%, color-coded according to their classification of evolutionary dynamics. Green elements represent CpG islands that have low rates of C–>T deamination and are typically unmethylated. Red elements represent CpG rich regions that gain G/C quickly and are in many cases constitutively methylated. Blue elements represent CpG rich loci that overlap exons (where stabilization of CpGs can be explained by indirect selective pressure on coding sequence). A probabilistic log-odds score for each CpG island indicates the specificity of the evolutionary behavior; positive values indicate hypo-deamination and negative values indicate high rates of G/C gain.

Clicking on the link will open the UCSC Genome browser on the HOXD gene cluster and will add the track to the display. In order to save the file, click on the Download link.

CpG island classification Download
CpG island classification (hg19) Download
CpG Islands Log Odds Score Download

 

Evolutionary dynamics

Following is a list of bigWig tracks containing observed and expected evolutionary dynamics in 50bp resolution, smoothed over 2kb windows. Clicking on a link will open the UCSC Genome browser on the HOXD gene cluster and will add the track to the display. In order to save the file, click on the Download link.

Observed Deamination (C–>T substitutions) rate observed deamination rate  Download
Expected Deamination (CG–>TG or CG–>CA substitutions) rate expected deamination rate Download
Observed non-deamination rate (CG–>XG substitutions, X≠T) observed non-deamination CpG losing substitutions rate Download
Expected non-deamination rate (CG–>XG substitutions, X≠T) expected non-deamination CpG losing substitutions rate Download
Observed CpG gain rate (XG–>CG or CX–>CG substitutions) observed CpG gain rate Download
Expected CpG gain rate (CX–>CG or XG–>CG substitutions) expected CpG gain rate Download
Observed G/C loss rate (C/G–>A/T substitutions, excluding CpGs) observed G/C loss rate Download
Expected G/C loss rate (G/C–>A/T substitutions, excluding CpGs) expected G/C loss rate Download
Observed G/C gain rate (A/T–>G/C substitutions, excluding CpGs) observed G/C gain rate Download
Expected G/C gain rate (A/T –> G/C substitutions, excluding CpGs) expected G/C gain rate Download

Scripts

In order to assist in annotating genomic intervals with evolutionary classification we provide the following R script and annotation file
annotate_cg.r
T1.txt

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