Epigenome dynamics: a quantitative genetics perspective

Johannes, Frank; Colot, Vincent; Jansen, Ritsert C.

doi:10.1038/nrg2467

Cited by 184 publications

(180 citation statements)

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“…Our analysis shows that CG epimutations are about five orders of magnitude more frequent than genetic mutations in A. thaliana [∼ 10 −4 compared with ∼ 10 −9 (25)] and are subject to forward-backward dynamics that are rarely observed for genetic loci. Because of these properties, it is intuitively obvious that these epimutation dynamics will lead to an uncoupling of epigenetic from genetic variation over relatively short evolutionary timescales (26). Simple deterministic models show that in a strictly selfing system without selection it would require only about 800 generations to reduce correlations between genotype and epigenotype from unity to below 0.5, We assume that an unmethylated cytosine (c u ) can become methylated (c m ) with probability α, and likewise a methylated cytosine can become unmethylated with probability β.…”

Section: Cg Epimutation Rates Are High Enough To Rapidly Uncouple Genmentioning

confidence: 99%

Rate, spectrum, and evolutionary dynamics of spontaneous epimutations

Graaf

Wardenaar

Neumann

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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258

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Stochastic changes in cytosine methylation are a source of heritable epigenetic and phenotypic diversity in plants. Using the model plant Arabidopsis thaliana, we derive robust estimates of the rate at which methylation is spontaneously gained (forward epimutation) or lost (backward epimutation) at individual cytosines and construct a comprehensive picture of the epimutation landscape in this species. We demonstrate that the dynamic interplay between forward and backward epimutations is modulated by genomic context and show that subtle contextual differences have profoundly shaped patterns of methylation diversity in A. thaliana natural populations over evolutionary timescales. Theoretical arguments indicate that the epimutation rates reported here are high enough to rapidly uncouple genetic from epigenetic variation, but low enough for new epialleles to sustain long-term selection responses. Our results provide new insights into methylome evolution and its population-level consequences.epigenetics | epimutation | DNA methylation | evolution | Arabidopsis P lant genomes make extensive use of cytosine methylation to control the expression of transposable elements (TEs) and genes (1). Despite its tight regulation, methylation losses or gains at individual cytosines or clusters of cytosines can emerge spontaneously, in an event termed "epimutation" (2, 3). Many examples of segregating epimutations have been documented in experimental and wild populations of plants and in some cases contribute to heritable variation in phenotypes independently of DNA sequence variation (4, 5). These observations have led to much speculation about the role of DNA methylation in plant evolution (6-8), and its potential in breeding programs (9). In the model plant Arabidopsis thaliana, spontaneous methylation changes at CG dinucleotides accumulate in a rapid but nonlinear fashion over generations (2,3,10), thus pointing to high forward-backward epimutation rates (11). Precise estimates of these rates are necessary to be able to quantify the long-term dynamics of epigenetic variation under laboratory or natural conditions, and to understand the molecular mechanisms that drive methylome evolution (12-14). Here we combine theoretical modeling with high-resolution methylome analysis of multiple independent A. thaliana mutation accumulation (MA) lines (15), including measurements of methylation changes in continuous generations, to obtain robust estimates of forward and backward epimutation rates. ResultsWe joined whole-genome MethylC-seq (16) data from two earlier MA studies (2, 3) with extensive multigenerational MethylC-seq measurements from three additional MA lines (Fig. 1A and SI Appendix, Tables S1-S6). The first of these new MA lines (MA1 3) was propagated for 30 generations and includes measurements for 13 (nearly) consecutive generations (Fig. 1A). The other two MA lines (MA2 3) were propagated for 17 generations and were measured every four generations on average (Fig. 1A). These new data therefore allowed us to track epimutation...

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Section: Cg Epimutation Rates Are High Enough To Rapidly Uncouple Genmentioning

confidence: 99%

Rate, spectrum, and evolutionary dynamics of spontaneous epimutations

Graaf

Wardenaar

Neumann

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

258

278

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“…The phenotypic response to environmental change is thought to include nongenetic, transgenerational processes (Bonduriansky and Day, 2009) that likely integrate epigenetic and/or maternal factors (Johannes et al, 2008;Danchin et al, 2011). Although maternal effects have been shown to influence these plant responses (Galloway, 2005), the involvement of organellar processes has not been formally demonstrated.…”

mentioning

confidence: 99%

The Chloroplast Triggers Developmental Reprogramming When MUTS HOMOLOG1 Is Suppressed in Plants

Santamaria

Virdi

et al. 2012

Plant Physiology

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Multicellular eukaryotes demonstrate nongenetic, heritable phenotypic versatility in their adaptation to environmental changes. This inclusive inheritance is composed of interacting epigenetic, maternal, and environmental factors. Yet-unidentified maternal effects can have a pronounced influence on plant phenotypic adaptation to changing environmental conditions. To explore the control of phenotypy in higher plants, we examined the effect of a single plant nuclear gene on the expression and transmission of phenotypic variability in Arabidopsis (Arabidopsis thaliana). MutS HOMOLOG1 (MSH1) is a plant-specific nuclear gene product that functions in both mitochondria and plastids to maintain genome stability. RNA interference suppression of the gene elicits strikingly similar programmed changes in plant growth pattern in six different plant species, changes subsequently heritable independent of the RNA interference transgene. The altered phenotypes reflect multiple pathways that are known to participate in adaptation, including altered phytohormone effects for dwarfed growth and reduced internode elongation, enhanced branching, reduced stomatal density, altered leaf morphology, delayed flowering, and extended juvenility, with conversion to perennial growth pattern in short days. Some of these effects are partially reversed with the application of gibberellic acid. Genetic hemicomplementation experiments show that this phenotypic plasticity derives from changes in chloroplast state. Our results suggest that suppression of MSH1, which occurs under several forms of abiotic stress, triggers a plastidial response process that involves nongenetic inheritance.

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“…We suggest that terms including the effects of reset and epigenetic transmissibility be included in the classical model of phenotypic variance, showing how these terms can be calculated from the covariances between relatives. Morphological and physiological phenotypes can be assessed in this way, and if the results point to an epigenetic component of inheritance, the underlying epigenomic bias can be investigated by employing QTL and association studies (Johannes et al 2008;Reinders et al 2009). A recent study using these methods provides evidence that epigenetic variation can contribute significantly to the heritability of complex traits ($30% heritability), introducing transgenerational stability of epialleles into quantitative genetic analysis ( Johannes et al 2009).…”

mentioning

confidence: 99%

“…Epigenetic inheritance occurs between generations of asexually and sexually reproducing organisms, directly affecting the hereditary structure of populations and providing a potential mechanism for their evolution (Jablonka andLamb 1995, 2005;Bonduriansky and Day 2009;Jablonka and Raz 2009;Verhoeven et al 2009). It is therefore necessary to develop tools to study its prevalence and estimate its contribution to the heritable variance in the population (Bossdorf et al 2008;Johannes et al 2008Johannes et al , 2009Richards 2008;Reinders et al 2009;Teixeira et al 2009). …”

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confidence: 99%

Epigenetic Contribution to Covariance Between Relatives

2010

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Recent research has pointed to the ubiquity and abundance of between-generation epigenetic inheritance. This research has implications for assessing disease risk and the responses to ecological stresses and also for understanding evolutionary dynamics. An important step toward a general evaluation of these implications is the identification and estimation of the amount of heritable, epigenetic variation in populations. While methods for modeling the phenotypic heritable variance contributed by culture have already been developed, there are no comparable methods for nonbehavioral epigenetic inheritance systems. By introducing a model that takes epigenetic transmissibility (the probability of transmission of ancestral phenotypes) and environmental induction into account, we provide novel expressions for covariances between relatives. We have combined a classical quantitative genetics approach with information about the number of opportunities for epigenetic reset between generations and assumptions about environmental induction to estimate the heritable epigenetic variance and epigenetic transmissibility for both asexual and sexual populations. This assists us in the identification of phenotypes and populations in which epigenetic transmission occurs and enables a preliminary quantification of their transmissibility, which could then be followed by genomewide association and QTL studies.

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Epigenome dynamics: a quantitative genetics perspective

Cited by 184 publications

References 52 publications

Rate, spectrum, and evolutionary dynamics of spontaneous epimutations

Rate, spectrum, and evolutionary dynamics of spontaneous epimutations

The Chloroplast Triggers Developmental Reprogramming When MUTS HOMOLOG1 Is Suppressed in Plants

Epigenetic Contribution to Covariance Between Relatives

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