Hydroxymethylated Cytosines Are Associated with Elevated C to G Transversion Rates

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Most cytosines that occur in a CpG context in mammalian genomes are methylated. Methylation has important functional consequences in the cell but also affects genome evolution. Notably, methylated cytosines are prone to deaminate and constitute mutational hotspots in mammalian genomes. Recently, a series of other modifications, derived from the oxidation of methylated cytosines, was shown to exist in various mammalian cell types including embryonic stem cells. The most abundant of these modifications is 5-hydroxymethylcytosine. In this work, we ask whether methylated and hydroxymethylated cytosines are subject to the same mutational biases or lead to distinct patterns of genome evolution. To do so, we examine differences between individuals, between species, and between normal and cancer tissues alongside high-resolution maps of DNA methylation and hydroxymethylation in the human and mouse genomes. Unexpectedly, we find that hydroxymethylated cytosines are associated with more cytosine to guanine changes in both human and mouse populations, in closely related species, and in the context of somatic evolution in tumors. Based on multiple lines of evidence, we suggest that the different patterns of sequence evolution at methylated and hydroxymethylated sites are owing to differences in how these sites are handled by the DNA repair machinery.

Vyšlo v časopise: Hydroxymethylated Cytosines Are Associated with Elevated C to G Transversion Rates. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004585
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004585

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