Mapping the Epigenetic Basis of Complex Traits

Cortijo, Sandra; Wardenaar, René; Colomé-Tatché, Maria; Gilly, Arthur; Etcheverry, Mathilde; Labadie, Karine; Caillieux, Erwann; Hospital, Frederic F.; Aury, Jean‐Marc; Wincker, Patrick; Roudier, François; Jansen, Ritsert C.; Colot, Vincent; Johannes, Frank

doi:10.1126/science.1248127

Cited by 429 publications

(449 citation statements)

References 26 publications

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“…A combination of incomplete resetting and maternal induction should be manifested as environmental effects on epigenotype and phenotype that persists over several generations, the magnitude of which may depend on the maternal or offspring environment, or both. Such effects are increasingly observed in animals and, in particular, plants (reviews in [4,5,17,19,42]), where studies of experimental lines suggest that induced patterns of DNA methylation are readily inherited [11]. Similarly, in mammals, DNA sequences can resist reprogramming [43,44], and the extent of demethylation is regulated by the methylation machinery [45,46].…”

Section: Discussionmentioning

confidence: 99%

“…Recent data from both animals and plants indicate that epigenetic resetting is not always complete and hence that acquired epigenetic states may be transmitted from parents to offspring ('germ-line epigenetic inheritance' or 'incomplete epigenetic resetting' or 'incomplete epigenetic reprogramming'; e.g. [6][7][8][9][10][11][12][13][14] reviewed in [4,5,[15][16][17][18][19]). …”

Section: Introductionmentioning

confidence: 99%

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When is incomplete epigenetic resetting in germ cells favoured by natural selection?

2015

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Resetting of epigenetic marks, such as DNA methylation, in germ cells or early embryos is not always complete. Epigenetic states may therefore persist, decay or accumulate across generations. In spite of mounting empirical evidence for incomplete resetting, it is currently poorly understood whether it simply reflects stochastic noise or plays an adaptive role in phenotype determination. Here, we use a simple model to show that incomplete resetting can be adaptive in heterogeneous environments. Transmission of acquired epigenetic states prevents mismatched phenotypes when the environment changes infrequently relative to generation time and when maternal and environmental cues are unreliable. We discuss how these results may help to interpret the emerging data on transgenerational epigenetic inheritance in plants and animals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

When is incomplete epigenetic resetting in germ cells favoured by natural selection?

2015

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“…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)(7)(8), and its potential in breeding programs (9).…”

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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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257

278

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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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“…These effects were accompanied by altered DNA methylation patterns in the germline (Anway et al, 2005;Jirtle and Skinner, 2007;Stouder and Paoloni-Giacobino, 2010). In the plant Arabidopsis, epigenetic inheritance can occur over at least eight generations (Johannes et al, 2009;Cortijo et al, 2014). In the nematode worm Caenorhabditis elegans, stable transmission across generations depends on gene regulation by microRNA (Rechavi, 2014).…”

Section: Epigeneticsmentioning

confidence: 99%

Why are individuals so different from each other?

Bateson

2014

Heredity

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An important contributor to the differences between individuals derives from their plasticity. Such plasticity is widespread in organisms from the simple to the most complex. Adaptability plasticity enables the organism to cope with a novel challenge not previously encountered by its ancestors. Conditional plasticity appears to have evolved from repeated challenges from the environment so that the organism responds in a particular manner to the environment in which it finds itself. The resulting phenotypic variation can be triggered during development in a variety of ways, some mediated through the parent's phenotype. Sometimes the organism copes in suboptimal conditions trading off reproductive success against survival. Whatever the adaptedness of the phenotype, each of the many types of plasticity demonstrates how a given genotype will express itself differently in different environmental conditions-a field of biology referred to as the study of epigenetics. The ways in which epigenetic mechanisms may have evolved are discussed, as are the potential impacts on the evolution of their descendants.

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Mapping the Epigenetic Basis of Complex Traits

Cited by 429 publications

References 26 publications

When is incomplete epigenetic resetting in germ cells favoured by natural selection?

When is incomplete epigenetic resetting in germ cells favoured by natural selection?

Rate, spectrum, and evolutionary dynamics of spontaneous epimutations

Why are individuals so different from each other?

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