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Transgenerational epigenetic instability is a source of novel methylation variants.
Science. 2011 Oct 21; 334(6054):369-73
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26 Sep 2011
New Finding
DOI: 10.3410/f.13292957.14652055
This interesting article shows that cytosine DNA methylation, thought to be primarily employed for gene silencing, is used in Arabidopsis for generating new allelic states, essentially producing phenotypic diversity in new generations without altering the genetic information.
Disclosures
None declared
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Deng X and Kong Y: F1000Prime Recommendation of [Schmitz RJ et al., Science 2011, 334(6054):369-73]. In F1000Prime, 26 Sep 2011; DOI: 10.3410/f.13292957.14652055. F1000Prime.com/13292957#eval14652055
29 Sep 2011
New Finding
DOI: 10.3410/f.13292957.14654054
This article shows that changes in the DNA methylation pattern of Arabidopsis can occur over 30 generations of selfing and plant growth under uniform conditions. These new epialleles can show altered transcription of the gene they are associated with. This spontaneous transgenerational change in DNA methylation...Continue reading
This article shows that changes in the DNA methylation pattern of Arabidopsis can occur over 30 generations of selfing and plant growth under uniform conditions. These new epialleles can show altered transcription of the gene they are associated with. This spontaneous transgenerational change in DNA methylation can provide phenotypic variability.
In this paper, the epigenomic consequences of single seed descent from a single ancestor over 30 generations of uniform growth are analysed. The methylome of three ancestral lines and five descendant lines is provided at single base resolution by bisulfite sequencing. 91% of methylated CpG sites (meCpGs) were maintained unchanged across all eight lines.
On average, 66,000 altered meCpGs are seen in each line. This led to the estimation of a lower limit of an epimutation rate of 4.46x10-4 methylation polymorphisms per CpG site per generation. Clustering of meCs revealed differentially methylated regions (DMRs) in the genome that were mainly associated with genic regions. The transcriptional activity of eight DMRs was measured, and in four of these there was an inverse correlation between level of methylation and transcriptional activity, indicating that the methylation level affected gene activity. 24nt-small interfering RNAs (siRNAs) were present at each silenced epiallele, indicating the involvement of the RNA-directed DNA methylation (RdDM) pathway.
The finding of such a high spontaneous epimutation rate (much higher than the mutation rate, and epiallele formation was independent of the base alteration mutation rate) suggests a source of genetic variability in plant species that may well have been selected for in crop production systems.
In this paper, the epigenomic consequences of single seed descent from a single ancestor over 30 generations of uniform growth are analysed. The methylome of three ancestral lines and five descendant lines is provided at single base resolution by bisulfite sequencing. 91% of methylated CpG sites (meCpGs) were maintained unchanged across all eight lines.
On average, 66,000 altered meCpGs are seen in each line. This led to the estimation of a lower limit of an epimutation rate of 4.46x10-4 methylation polymorphisms per CpG site per generation. Clustering of meCs revealed differentially methylated regions (DMRs) in the genome that were mainly associated with genic regions. The transcriptional activity of eight DMRs was measured, and in four of these there was an inverse correlation between level of methylation and transcriptional activity, indicating that the methylation level affected gene activity. 24nt-small interfering RNAs (siRNAs) were present at each silenced epiallele, indicating the involvement of the RNA-directed DNA methylation (RdDM) pathway.
The finding of such a high spontaneous epimutation rate (much higher than the mutation rate, and epiallele formation was independent of the base alteration mutation rate) suggests a source of genetic variability in plant species that may well have been selected for in crop production systems.
Disclosures
None declared
Dennis E: F1000Prime Recommendation of [Schmitz RJ et al., Science 2011, 334(6054):369-73]. In F1000Prime, 29 Sep 2011; DOI: 10.3410/f.13292957.14654054. F1000Prime.com/13292957#eval14654054
28 Nov 2011
New Finding
DOI: 10.3410/f.13292957.14740090
Spontaneously occurring epigenetic variation was tracked in Arabidopsis lines produced by 30 generations of ‘selfing’ in single-seed progeny. Single CG (cytosine-guanine) methylation polymorphisms and differentially methylated regions showed non-ancestral patterns in many instances. The authors speculate...Continue reading
Spontaneously occurring epigenetic variation was tracked in Arabidopsis lines produced by 30 generations of ‘selfing’ in single-seed progeny. Single CG (cytosine-guanine) methylation polymorphisms and differentially methylated regions showed non-ancestral patterns in many instances. The authors speculate that such epialleles can lead to phenotypic changes in the absence of mutations. Spontaneous DNA mutations had also been tracked in these lines. It would be interesting to see if the DNA and methylation alterations that were tracked in these lines correlated in any way.
Disclosures
None declared
Sinha N: F1000Prime Recommendation of [Schmitz RJ et al., Science 2011, 334(6054):369-73]. In F1000Prime, 28 Nov 2011; DOI: 10.3410/f.13292957.14740090. F1000Prime.com/13292957#eval14740090
13 Dec 2011
New Finding
DOI: 10.3410/f.13292957.14775095
The authors generated single nucleotide resolution maps of DNA methylation in three ancestral and five descendant Arabidopsis thaliana lines separated by 30 generations. They demonstrated that ~1.62% of the CG methylation shows polymorphisms, either gain or loss of the cytosine methylation, within the...Continue reading
The authors generated single nucleotide resolution maps of DNA methylation in three ancestral and five descendant Arabidopsis thaliana lines separated by 30 generations. They demonstrated that ~1.62% of the CG methylation shows polymorphisms, either gain or loss of the cytosine methylation, within the descendant lines. The authors reported a total of 2485 inheritable CG-DMRs (differentially methylated regions) and 72 C-DMRs (DMRs that include CG, CHG, and CHH methylation polymorphisms). Interestingly, increase/decrease of mRNA and small RNA was associated with gain/loss of DNA methylation of several C-DMRs.
Numerous epigenetic mutations, caused mostly by DNA methylation changes, have been reported in different organisms. Nevertheless, the frequency of spontaneous gain or loss of DNA methylation through different generations has been unknown. For the first time, this paper demonstrates that spontaneous DNA methylation changes occur more frequently than genetic changes and can alter gene expression. The next phase of this exciting research would be mapping methylation changes associated with plants grown under stress conditions, such as drought or salt stress, which would provide further insight on the impact of epigenetic mutation on plant adaptation and evolution.
Numerous epigenetic mutations, caused mostly by DNA methylation changes, have been reported in different organisms. Nevertheless, the frequency of spontaneous gain or loss of DNA methylation through different generations has been unknown. For the first time, this paper demonstrates that spontaneous DNA methylation changes occur more frequently than genetic changes and can alter gene expression. The next phase of this exciting research would be mapping methylation changes associated with plants grown under stress conditions, such as drought or salt stress, which would provide further insight on the impact of epigenetic mutation on plant adaptation and evolution.
Disclosures
None declared
Jiang J: F1000Prime Recommendation of [Schmitz RJ et al., Science 2011, 334(6054):369-73]. In F1000Prime, 13 Dec 2011; DOI: 10.3410/f.13292957.14775095. F1000Prime.com/13292957#eval14775095
10 Jan 2012
New Finding
DOI: 10.3410/f.13292957.14811090
Using high-throughput, whole-genome sequencing technologies, the authors examined the frequency at which variation in naturally occurring DNA methylation, or epimutation, occurs in Arabidopsis thaliana. By comparing methylomes and sRNAomes between ancestral and descendant populations, the authors observed...Continue reading
Using high-throughput, whole-genome sequencing technologies, the authors examined the frequency at which variation in naturally occurring DNA methylation, or epimutation, occurs in Arabidopsis thaliana. By comparing methylomes and sRNAomes between ancestral and descendant populations, the authors observed a high epimutation rate. The authors have also provided evidence that transgenerational epigenetic variation conferred by cytosine DNA methylation may play a role in the generation of sequence-independent epialleles. This mechanism can provide means for phenotypic diversity in the absence of genetic mutations and, hence, potentially play an important role in plant evolution. For further reading, please see ref {1}.
References
1.
Whole-genome sequencing of multiple Arabidopsis thaliana populations.
Nat Genet 2011 Oct; 10(43):956-63
PMID: 21874002
Disclosures
None declared
Pontes O and Costa-Nunes P: F1000Prime Recommendation of [Schmitz RJ et al., Science 2011, 334(6054):369-73]. In F1000Prime, 10 Jan 2012; DOI: 10.3410/f.13292957.14811090. F1000Prime.com/13292957#eval14811090
28 Feb 2012
New Finding
DOI: 10.3410/f.13292957.15405120
This landmark paper provides insight into how DNA methylation patterns change over time by bisulfite sequencing a number of mutation accumulation lines, as well as the founders. The rates observed are sufficiently high for epialleles to be a significant contribution to variation. This paper should be...Continue reading
This landmark paper provides insight into how DNA methylation patterns change over time by bisulfite sequencing a number of mutation accumulation lines, as well as the founders. The rates observed are sufficiently high for epialleles to be a significant contribution to variation. This paper should be read in parallel with Becker et al. {1}, who reach similar conclusions with similar data.
References
1.
Spontaneous epigenetic variation in the Arabidopsis thaliana methylome.
Nature 2011 Dec 8; 7376(480):245-9
PMID: 22057020
Disclosures
None declared
Nordborg M: F1000Prime Recommendation of [Schmitz RJ et al., Science 2011, 334(6054):369-73]. In F1000Prime, 28 Feb 2012; DOI: 10.3410/f.13292957.15405120. F1000Prime.com/13292957#eval15405120
F1000Prime Recommendations, Dissents and Comments for [Schmitz RJ et al., Science 2011, 334(6054):369-73]. In F1000Prime, 22 May 2013; F1000Prime.com/13292957
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Epigenetic information, which may affect an organism's phenotype, can be stored and stably inherited in the form of cytosine DNA methylation. Changes in DNA methylation can produce meiotically stable epialleles that affect transcription and morphology, but the rates of spontaneous gain or loss of DNA methylation are unknown. We examined spontaneously occurring variation in DNA methylation in Arabidopsis thaliana plants propagated by single-seed descent for 30 generations. We identified 114,287 CG single methylation polymorphisms and 2485 CG differentially methylated regions (DMRs), both of which show patterns of divergence compared with the ancestral state. Thus, transgenerational epigenetic variation in DNA methylation may generate new allelic states that alter transcription, providing a mechanism for phenotypic diversity in the absence of genetic mutation.
PMID: 21921155
