AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants
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AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants Yadollah Shahryary1,2 , Aikaterini Symeonidi1 , Rashmi R. Hazarika1,2 , Johanna Denkena3 , Talha Mubeen1,2 , Brigitte Hofmeister4 , Thomas van Gurp7 , Maria Colomé-Tatché3,5,6 , Koen J.F. Verhoeven7 , Gerald Tuskan8 , Robert J. Schmitz2,9* and Frank Johannes1,2* *Correspondence: [email protected]; [email protected] 1 Technical University of Munich, Department of Plant Sciences, Liesel-Beckmann-Str. 2, 85354 Freising, Germany 2 Technical University of Munich, Institute for Advanced Study, Lichtenbergstr. 2a, 85748 Garching, Germany Full list of author information is available at the end of the article
Abstract Stochastic changes in DNA methylation (i.e., spontaneous epimutations) contribute to methylome diversity in plants. Here, we describe AlphaBeta, a computational method for estimating the precise rate of such stochastic events using pedigree-based DNA methylation data as input. We demonstrate how AlphaBeta can be employed to study transgenerationally heritable epimutations in clonal or sexually derived mutation accumulation lines, as well as somatic epimutations in long-lived perennials. Application of our method to published and new data reveals that spontaneous epimutations accumulate neutrally at the genome-wide scale, originate mainly during somatic development and that they can be used as a molecular clock for age-dating trees. Keywords: Epimutation, DNA methylation, Plants, Trees, Epigenetics, Epimutation rate, Evolution, Molecular clock, Epigenetic clock, Bioinformatics software tool, R/Bioconductor package
Introduction Cytosine methylation is an important chromatin modification and a pervasive feature of most plant genomes. It has major roles in the silencing of transposable elements (TEs) and repeat sequences and is also involved in the regulation of some genes [1]. Plants methylate cytosines at symmetrical CG and CHG sites, but also extensively at asymmetrical CHH sites, where H= A, T, C. The molecular pathways that establish and maintain methylation in these three sequence contexts are well-characterized [2] and are broadly conserved across plant species [3–7]. Despite its tight regulation, the methylation status of individual cytosines or of clusters of cytosines is not always faithfully maintained across
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