Region-level epimutation rates in Arabidopsis thaliana

Abstract

Failure to maintain DNA methylation patterns during plant development can occasionally give rise to so-called “spontaneous epimutations”. These stochastic methylation changes are sometimes heritable across generations and thus accumulate in plant genomes over time. Recent evidence indicates that spontaneous epimutations have a major role in shaping patterns of methylation diversity in plant populations. Using single CG dinucleotides as units of analysis, previous work has shown that the epimutation rate is several orders of magnitude higher than the genetic mutation rate. While these large rate differences have obvious implications for understanding genome-methylome co-evolution, the functional relevance of single CG methylation changes remains questionable. In contrast to single CG, solid experimental evidence has linked methylation gains and losses in larger genomic regions with transcriptional variation and heritable phenotypic effects. Here we show that such region-level changes arise stochastically at about the same rate as those at individual CG sites, are only marginal dependent on region size and cytosine density, but strongly dependent on chromosomal location. We also find consistent evidence that region-level epimutations are not restricted to CG contexts but also frequently occur in non-CG regions at the genome-wide scale. Taken together, our results support the view that many differentially methylated regions (DMRs) in natural populations originate from epimutation events and may not be effectively tagged by proximal SNPs. This possibility reinforces the need for epigenome-wide association studies (EWAS) in plants as a way to identify the epigenetic basis of complex traits.

Epigenome and Epitranscriptome: Potential Resources for Crop Improvement

“…Like genetic mutations, spontaneous somatic epimutations are common and the epimutation rate at CG dinucleotides is much higher than the genetic mutation rate [ 101 ]. The region-level epimutation rate is not linked to genetic mutations but depends on the chromosomal location, where chromosome arms and the centromere display the highest and lowest epimutation rates, respectively [ 106 ]. Genetic changes could lead to large-scale epigenetic changes and the resulting epimutation can be maintained even after the genetic change is lost [ 103 ].…”

Re-analysis of publicly available methylomes using signal detection yields new information

“…Variation is thought to arise from thermodynamic fluctuations of cellular machinery and the DNA molecule itself 5 , 19 – 22 . There is inherent stochasticity to methylome remodeling with each cell division, giving rise to ‘spontaneous epimutations’ in all methylation contexts 18 , 23 , 24 . Noise in BS-seq datasets is also amplified by tissue pooling as the plant epigenome appears to be developmental stage-, tissue- and cell-type specific 25 – 31 .…”

The effects of mutations on gene expression and alternative splicing: a case study of EMS-induced heritable mutations in the microcrustaceanDaphnia

“…To date, many MA studies have moved beyond simply measuring the mutation rate, spectrum, and fitness effects on the organismal level. For example, MA studies have been utilized to study transposable element mutation rates (Díaz-González andDomínguez 2020, Ho et al 2021), enzymatic activity (Aquadro et al 1990, Harada 1995, methylation frequency (Denkena et al 2021, Jiang et al 2014, phenotypic plasticity (Latta et al 2015), and patterns of genotype-environment interactions (Chu and Zhang 2021, Scheffer et al 2022, Xu 2004).…”