This is an interesting paper as it looks at the question as to what extent DNA methylation results in DNA mutation which then results in less methylation.
https://www.nature.com/articles/s43587-024-00794-x
Obviously this is potentially a big issue as it implies that genes which are methylated end up being mutated which is harder to fix than methylation which merely needs a TET enzyme.
There is an element to which DNA has forms of check digits in it which can be used to fix mutation. I have not reviewed this in detail, but there clearly is something there.
I have contacted the author of the paper to ask what proportion of methylated sites end up mutated.
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From chatgpt without reviewing for accuracy
Methylated DNA is more prone to mutations, particularly at CpG sites, where cytosine (C) is methylated to 5-methylcytosine (5mC). The most common mutation occurs when 5mC deaminates to thymine (T), leading to a C→T transition.
Proportion of Mutations at Methylated Sites:
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CpG sites mutate 10–50 times more frequently than non-methylated sites.
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About one-third of all point mutations in the human genome occur at methylated CpG sites.
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80–90% of CpG sites in vertebrates are methylated, making them mutation hotspots.
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C→T transitions at CpG sites account for about 25–30% of disease-causing mutations in humans.
In summary, methylation significantly increases the likelihood of mutations, particularly C→T transitions, making CpG sites one of the most mutation-prone regions in the genome.
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