CpG islands and their methylation patterns are the epigeneticists bread and butter, and it’s been assumed by many that there are evolutionary reasons behind their existence. New data suggests that not all CpG islands were created equal, and much like Donald Trump’s hair, can’t entirely be explained by natural selection.
High-powered researchers from the Weizmann Institute of Science in Israel developed new evolutionary models, combined with meta-analysis of DNA methylation data to study primate genomes, and decipher the origins of CpG islands. Their work uncovered at least three major evolutionary modes controlling the creation and upkeep of CpG-rich genomic regions.
Regions of Slow C-to-T Deamination
The majority of CpG islands are normally unmethylated and undergo slow C-to-T deamination. CpG stability in these elements can be explained by the neutral effect of slow deamination alone, that goes with the lack of methylation, with no evidence of selection on CpG densities going on.
Biased Gene Conversion CpGs
Regions called biased gene conversion (BGC) CpG islands, are constitutively methylated and clustered in subtelomeric regions. These elements deaminate quickly, but also gain CpGs rapidly leading to high stationary CpG content. So, their evolutionary origins can also be accounted for without selection. BGC CpG islands don’t match with the original notion of CpG islands (unmethylated regions that are typically found near gene promoters), and their current grouping with the classical unmethylated is misleading.
Areas Losing CpGs
A third type evolutionary dynamics involves elements with decaying CpG content. These regions are typically methylated and may be sequences that were previously protected from methylation or underwent biased gene conversion, but then lost the mechanism stabilizing their CpG content.
These three evolutionary regimes, combined with exonic CpG islands and repetitive elements, form a new framework for understanding patterns of DNA methylation in the human genome that the authors believe will become more and more important as more epigenetic profiles continue to be generated.
Read the full article and join the revolution at Cell, May 2011.