Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

<jats:p>Methylated cytosines deaminate at higher rates than unmethylated cytosines and the lesions they produce are repaired less efficiently. As a result, methylated cytosines are mutational hotspots. Here, combining rare polymorphism and base-resolution methylation data in human, <jats:italic>Arabidopsis thaliana</jats:italic>, and rice (<jats:italic>Oryza sativa</jats:italic>), we present evidence that methylation state affects mutation dynamics not only at the focal cytosine but also at neighbouring nucleotides. In human, contrary to prior suggestions, we find that nucleotides in the close vicinity (±3bp) of methylated cytosines mutate less frequently. Reduced mutability around methylated CpGs is also observed in cancer genomes, considering single nucleotide variants alongside tissue-of-origin-matched methylation data. In contrast, methylation is associated with increased neighbourhood mutation risk in <jats:italic>A. thaliana</jats:italic> and rice. The difference in neighbourhood mutation risk is less pronounced further away from the focal CpG and modulated by regional GC content. Our results are consistent with a model where altered risk at neighbouring bases is linked to lesion formation at the focal CpG and subsequent long-patch repair. Our findings indicate that cytosine methylation has a broader mutational footprint than is commonly assumed.</jats:p>

Original publication




Journal article




Genetics Society of America

Publication Date



genetics.303028.2020 - genetics.303028.2020