Figure 1.
Evidence of Purifying Selection Operating on Promoter Epivariations
(A) Using pLI scores generated by the ExAC,5 we observed that hypermethylated promoter epivariations were preferentially associated with genes showing reduced selective constraint (permutation p < 10−7). Similarly, hypomethylated epivariations were also biased away from genes with high pLI scores, but to a lesser degree (permutation p = 1.6 × 10−3).
(B) We observed an inverse relationship between the population frequency of hypermethylated promoter epivariations and selective constraint of the associated gene (Pearson p = 1.8 × 10−6). These distributions are consistent with many promoter epivariations undergoing purifying selection which acts to reduce their frequency in the population. The red dot shows the mean pLI score in each distribution.