<scp>DNA</scp>
            Methylation and Mutation

Pfeifer, Gerd P.

doi:10.1002/9780470015902.a0006159.pub2

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…Conversely, TEs, for which mobility across the genome is controlled by DNA methylation, can affect genetic variation [15]. Methylation is also known to affect DNA mutation rates [82] and, therefore, DNA polymorphism as a result of the spontaneous deamination of mC [83]. As underlined by our study, the diversity of epigenetic interactions with genetic variation limits our interpretation of how epigenetic mechanisms shape DNA methylation variation at the level of genetically diverse groups (e.g., populations and lines).…”

Section: Discussionmentioning

confidence: 99%

Assessing Global DNA Methylation Changes Associated with Plasticity in Seven Highly Inbred Lines of Snapdragon Plants (Antirrhinum majus)

Gourcilleau

Mousset

Latutrie

et al. 2019

Genes

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Genetic and epigenetic variations are commonly known to underlie phenotypic plastic responses to environmental cues. However, the role of epigenetic variation in plastic responses harboring ecological significance in nature remains to be assessed. The shade avoidance response (SAR) of plants is one of the most prevalent examples of phenotypic plasticity. It is a phenotypic syndrome including stem elongation and multiple other traits. Its ecological significance is widely acknowledged, and it can be adaptive in the presence of competition for light. Underlying genes and pathways were identified, but evidence for its epigenetic basis remains scarce. We used a proven and accessible approach at the population level and compared global DNA methylation between plants exposed to regular light and three different magnitudes of shade in seven highly inbred lines of snapdragon plants (Antirrhinum majus) grown in a greenhouse. Our results brought evidence of a strong SAR syndrome for which magnitude did not vary between lines. They also brought evidence that its magnitude was not associated with the global DNA methylation percentage for five of the six traits under study. The magnitude of stem elongation was significantly associated with global DNA demethylation. We discuss the limits of this approach and why caution must be taken with such results. In-depth approaches at the DNA sequence level will be necessary to better understand the molecular basis of the SAR syndrome.

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Section: Discussionmentioning

confidence: 99%

Assessing Global DNA Methylation Changes Associated with Plasticity in Seven Highly Inbred Lines of Snapdragon Plants (Antirrhinum majus)

Gourcilleau

Mousset

Latutrie

et al. 2019

Genes

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“…Methylation of the cytosine at CpG sites has important roles within the cell in regulating gene expression and silencing (Long et al, 2017). Single-gene and genome sequencing studies have identified that the vast majority of substitution mutations in human cancer occurs at the CpG dinucleotide (Cooper and Youssoufian, 1988;Esteller et al, 2001;Esteller, 2002;Poulos et al, 2017;Pfeifer, 2017). Genome-scale studies revealed that the most frequently methylated genes in cancer cells were genes encoding transcription factors (Pfeifer, 2018), which are specifically enriched in IDPs (Deiana et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Evolutionary forces on different flavors of intrinsic disorder in the human proteome

Forcelloni

Giansanti

2019

Preprint

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In this study, we perform a systematic analysis of evolutionary forces (i.e., mutational bias and natural selection) that shape the codon usage bias of human genes encoding for different structural and functional variants of proteins. Well-structured proteins are expected to be more under control by natural selection than intrinsically disordered proteins because one or few mutations (even synonymous) in the genes can result in a protein that no longer folds correctly. On the contrary, intrinsically disordered proteins are generally thought to evolve more rapidly than well-folded proteins, primarily attributed to relaxed purifying natural selection due to the lack of structural constraints. Using different genetic tools, we find compelling evidence that intrinsically disordered proteins are the variant of human proteins on which both mutational bias and natural selection act more effectively, corroborating their essential role for evolutionary adaptability and protein evolvability. We speculate that intrinsically disordered proteins have a high tolerance to mutations (both neutral and adaptive) but also a selective propensity to preserve their structural disorder, i.e., flexibility and conformational dynamics under physiological conditions. Additionally, we confirm not only that intrinsically disordered proteins are preferentially encoded by GC-rich genes, but also that they are characterized by the highest fraction of CpG-sites in the sequences, implying a higher susceptibility to methylation resulting in C-T transition mutations. Our results provide new insight about protein evolution and human genetic diseases identifying intrinsically disordered proteins as reservoirs for evolutionary innovations.

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“…The generation of an excess of de novo biased variants-i.e., more variants yielding A/Ts-at sites of minor grooves facing histones, would leave these sites enriched for these nucleotides over evolutionary time. De novo mutations detected in many species exhibit this bias due to the spontaneous deamination of cytosine and 5-methylcytosine (Long et al, 2018;Cooper et al, 2010;Pfeifer, 2017;Shen et al, 1994).…”

Section: A Role For Differential Mutation Rate In Genomic Sequence Pementioning

confidence: 99%

Somatic and Germline Mutation Periodicity Follow the Orientation of the DNA Minor Groove around Nucleosomes

Pich

Muiños

Sabarinathan

et al. 2018

Cell

110

154

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Graphical AbstractHighlights d Somatic and germline mutation rates show a 10-bp periodicity in nucleosome-occupied DNA d This periodicity tracks DNA minor groove facing toward and away from the histones d The orientation of the periodicity depends on the mutational processes active in the tissue d This has contributed to the AT/CG 10-bp periodicity in eukaryotic genomes SUMMARYMutation rates along the genome are highly variable and influenced by several chromatin features. Here, we addressed how nucleosomes, the most pervasive chromatin structure in eukaryotes, affect the generation of mutations. We discovered that within nucleosomes, the somatic mutation rate across several tumor cohorts exhibits a strong 10 base pair (bp) periodicity. This periodic pattern tracks the alternation of the DNA minor groove facing toward and away from the histones. The strength and phase of the mutation rate periodicity are determined by the mutational processes active in tumors. We uncovered similar periodic patterns in the genetic variation among human and Arabidopsis populations, also detectable in their divergence from close species, indicating that the same principles underlie germline and somatic mutation rates. We propose that differential DNA damage and repair processes dependent on the minor groove orientation in nucleosomebound DNA contribute to the 10-bp periodicity in AT/CG content in eukaryotic genomes.

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DNA Methylation and Mutation

Cited by 5 publications

References 42 publications

Assessing Global DNA Methylation Changes Associated with Plasticity in Seven Highly Inbred Lines of Snapdragon Plants (Antirrhinum majus)

Assessing Global DNA Methylation Changes Associated with Plasticity in Seven Highly Inbred Lines of Snapdragon Plants (Antirrhinum majus)

Evolutionary forces on different flavors of intrinsic disorder in the human proteome

Somatic and Germline Mutation Periodicity Follow the Orientation of the DNA Minor Groove around Nucleosomes

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