A Neutrality Test for Detecting Selection on DNA Methylation Using Single Methylation Polymorphism Frequency Spectrum

wang, jun ; fan,chuanzhu;

Inheritable epigenetic mutations (epimutations) can contribute to transmittable phenotypic variation. Thus, epimutations can be subject to natural selection and impact the fitness and evolution of organisms. Based on the framework of the modified Tajima’s Dtest for DNA mutations, we developed a neutrality test with the statistic “Dm” to detect selection force son DNA methylation mutations using single methylation poly morphisms. With computer simulation and empirical data analysis, we compared the Dm test with the original and modified Tajima’s D tests and demonstrated that the Dm test is suitable for detecting selection on epimutations and outperforms original/modified Tajima’s D tests. Due to the higher resetting rate of epimutations, the interpretation of Dm on epimutations and Tajima’s D test on DNA mutations could be different in inferring natural selection. Analyses using simulated and empirical genome-wide polymorphism data suggested that genesunder genetic andepigenetic selections behaved differently. We applied the Dm test to recently originated Arabidopsis and humangenes, and showed that newly evolved genes contain higher level of rare epialleles, suggesting that epimutation may play a role in origination and evolution of genes and genomes. Overall, we demonstrate the utility of the Dm test to detect whether the lociare under selection regarding DNA methylation.Our analytical metric sand methodology could contribute to our understanding of evolutionary processes of genes and genomes in the field of epigenetics.The Perl script for the “Dm” test is available at http://fanlab.wayne.edu/ (last accessed December 18, 2014)