AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants
Abstract
Stochastic changes in DNA methylation (i.e., spontaneous epimutations) contribute to methylome diversity in plants. Here, we describe AlphaBeta, a computational method for estimating the precise rate of such stochastic events using pedigree-based DNA methylation data as input. We demonstrate how AlphaBeta can be employed to study transgenerationally heritable epimutations in clonal or sexually derived mutation accumulation lines, as well as somatic epimutations in long-lived perennials. Application of our method to published and new data reveals that spontaneous epimutations accumulate neutrally at the genome-wide scale, originate mainly during somatic development and that they can be used as a molecular clock for age-dating trees.
- Authors:
-
- Technical Univ. of Munich (Germany). Dept. of Plant Sciences; Technical Univ. of Munich (Germany). Inst. for Advanced Study
- Technical Univ. of Munich (Germany). Dept. of Plant Sciences
- Helmholtz Zentrum München, Neuherberg (Germany). Inst. of Computational Biology
- Inst. of Bioinformatics, Athens (Greece)
- Netherlands Inst. of Ecology (NIOO-KNAW), Wageningen (Netherlands). Dept. of Terrestrial Ecology
- Helmholtz Zentrum München, Neuherberg (Germany). Inst. of Computational Biology; Univ. of Groningen (Netherlands). Univ. Medical Centre Groningen. European Research Inst. for the Biology of Ageing; Technical Univ. of Munich (Germany). TUM School of Life Sciences Weihenstephan
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Bioeneregy Innovation
- Technical Univ. of Munich (Germany). Inst. for Advanced Study; Univ. of Georgia, Athens, GA (United States). Dept. of Genetics
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1815907
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Genome Biology (Online)
- Additional Journal Information:
- Journal Name: Genome Biology (Online); Journal Volume: 21; Journal Issue: 1; Journal ID: ISSN 1474-760X
- Publisher:
- BioMed Central
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Epimutation; DNA methylation; Plants; Trees; Epigenetics; Epimutation rate; Evolution; Molecular clock; Epigenetic clock; Bioinformatics software tool; R/Bioconductor package
Citation Formats
Shahryary, Yadollah, Symeonidi, Aikaterini, Hazarika, Rashmi R., Denkena, Johanna, Mubeen, Talha, Hofmeister, Brigitte, van Gurp, Thomas, Colomé-Tatché, Maria, Verhoeven, Koen J. F., Tuskan, Gerald, Schmitz, Robert J., and Johannes, Frank. AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants. United States: N. p., 2020.
Web. doi:10.1186/s13059-020-02161-6.
Shahryary, Yadollah, Symeonidi, Aikaterini, Hazarika, Rashmi R., Denkena, Johanna, Mubeen, Talha, Hofmeister, Brigitte, van Gurp, Thomas, Colomé-Tatché, Maria, Verhoeven, Koen J. F., Tuskan, Gerald, Schmitz, Robert J., & Johannes, Frank. AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants. United States. https://doi.org/10.1186/s13059-020-02161-6
Shahryary, Yadollah, Symeonidi, Aikaterini, Hazarika, Rashmi R., Denkena, Johanna, Mubeen, Talha, Hofmeister, Brigitte, van Gurp, Thomas, Colomé-Tatché, Maria, Verhoeven, Koen J. F., Tuskan, Gerald, Schmitz, Robert J., and Johannes, Frank. Tue .
"AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants". United States. https://doi.org/10.1186/s13059-020-02161-6. https://www.osti.gov/servlets/purl/1815907.
@article{osti_1815907,
title = {AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants},
author = {Shahryary, Yadollah and Symeonidi, Aikaterini and Hazarika, Rashmi R. and Denkena, Johanna and Mubeen, Talha and Hofmeister, Brigitte and van Gurp, Thomas and Colomé-Tatché, Maria and Verhoeven, Koen J. F. and Tuskan, Gerald and Schmitz, Robert J. and Johannes, Frank},
abstractNote = {Stochastic changes in DNA methylation (i.e., spontaneous epimutations) contribute to methylome diversity in plants. Here, we describe AlphaBeta, a computational method for estimating the precise rate of such stochastic events using pedigree-based DNA methylation data as input. We demonstrate how AlphaBeta can be employed to study transgenerationally heritable epimutations in clonal or sexually derived mutation accumulation lines, as well as somatic epimutations in long-lived perennials. Application of our method to published and new data reveals that spontaneous epimutations accumulate neutrally at the genome-wide scale, originate mainly during somatic development and that they can be used as a molecular clock for age-dating trees.},
doi = {10.1186/s13059-020-02161-6},
journal = {Genome Biology (Online)},
number = 1,
volume = 21,
place = {United States},
year = {Tue Oct 06 00:00:00 EDT 2020},
month = {Tue Oct 06 00:00:00 EDT 2020}
}
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Works referenced in this record:
Low number of fixed somatic mutations in a long-lived oak tree
journal, December 2017
- Schmid-Siegert, Emanuel; Sarkar, Namrata; Iseli, Christian
- Nature Plants, Vol. 3, Issue 12
DNA Methylation Signatures of the Plant Chromomethyltransferases
journal, December 2016
- Gouil, Quentin; Baulcombe, David C.
- PLOS Genetics, Vol. 12, Issue 12
METHimpute: imputation-guided construction of complete methylomes from WGBS data
journal, June 2018
- Taudt, Aaron; Roquis, David; Vidalis, Amaryllis
- BMC Genomics, Vol. 19, Issue 1
Signatures of Dobzhansky–Muller Incompatibilities in the Genomes of Recombinant Inbred Lines
journal, December 2015
- Colomé-Tatché, Maria; Johannes, Frank
- Genetics, Vol. 202, Issue 2
Stable inheritance of DNA methylation allows creation of epigenotype maps and the study of epiallele inheritance patterns in the absence of genetic variation
journal, August 2017
- Hofmeister, Brigitte T.; Lee, Kevin; Rohr, Nicholas A.
- Genome Biology, Vol. 18, Issue 1
Transgenerational epimutations induced by multi-generation drought imposition mediate rice plant’s adaptation to drought condition
journal, January 2017
- Zheng, Xiaoguo; Chen, Liang; Xia, Hui
- Scientific Reports, Vol. 7, Issue 1
Epigenetic dynamics during flowering plant reproduction: evidence for reprogramming?
journal, May 2019
- Gehring, Mary
- New Phytologist, Vol. 224, Issue 1
epiGBS: reference-free reduced representation bisulfite sequencing
journal, February 2016
- van Gurp, Thomas P.; Wagemaker, Niels C. A. M.; Wouters, Björn
- Nature Methods, Vol. 13, Issue 4
The theory of inbreeding with forced heterozygosis
journal, October 1935
- Bartlett, M. S.; Haldane, J. B. S.
- Journal of Genetics, Vol. 31, Issue 3
Genetic sources of population epigenomic variation
journal, May 2016
- Taudt, Aaron; Colomé-Tatché, Maria; Johannes, Frank
- Nature Reviews Genetics, Vol. 17, Issue 6
Reprogramming of DNA Methylation in Pollen Guides Epigenetic Inheritance via Small RNA
journal, September 2012
- Calarco, Joseph P.; Borges, Filipe; Donoghue, Mark T. A.
- Cell, Vol. 151, Issue 1
Structural absorption by barbule microstructures of super black bird of paradise feathers
journal, January 2018
- McCoy, Dakota E.; Feo, Teresa; Harvey, Todd Alan
- Nature Communications, Vol. 9, Issue 1
Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome
journal, January 2013
- Stroud, Hume; Greenberg, Maxim V. C.; Feng, Suhua
- Cell, Vol. 152, Issue 1-2
Evolutionary patterns of genic DNA methylation vary across land plants
journal, January 2016
- Takuno, Shohei; Ran, Jin-Hua; Gaut, Brandon S.
- Nature Plants, Vol. 2, Issue 2
Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation
journal, April 2010
- Zemach, A.; McDaniel, I. E.; Silva, P.
- Science, Vol. 328, Issue 5980
Do plants have a segregated germline?
journal, May 2018
- Lanfear, Robert
- PLOS Biology, Vol. 16, Issue 5
DNA Methylation Clocks in Aging: Categories, Causes, and Consequences
journal, September 2018
- Field, Adam E.; Robertson, Neil A.; Wang, Tina
- Molecular Cell, Vol. 71, Issue 6
Diversity of cytosine methylation across the fungal tree of life
journal, February 2019
- Bewick, Adam J.; Hofmeister, Brigitte T.; Powers, Rob A.
- Nature Ecology & Evolution, Vol. 3, Issue 3
Human body epigenome maps reveal noncanonical DNA methylation variation
journal, June 2015
- Schultz, Matthew D.; He, Yupeng; Whitaker, John W.
- Nature, Vol. 523, Issue 7559
Epigenetic reprogramming in plant sexual reproduction
journal, July 2014
- Kawashima, Tomokazu; Berger, Frédéric
- Nature Reviews Genetics, Vol. 15, Issue 9
MethylStar: A fast and robust pre-processing pipeline for bulk or single-cell whole-genome bisulfite sequencing data
journal, July 2020
- Shahryary, Yadollah; Hazarika, Rashmi R.; Johannes, Frank
- BMC Genomics, Vol. 21, Issue 1
Methylome evolution in plants
journal, December 2016
- Vidalis, Amaryllis; Živković, Daniel; Wardenaar, René
- Genome Biology, Vol. 17, Issue 1
Widespread natural variation of DNA methylation within angiosperms
journal, September 2016
- Niederhuth, Chad E.; Bewick, Adam J.; Ji, Lexiang
- Genome Biology, Vol. 17, Issue 1
Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia
journal, May 2019
- Gaiti, Federico; Chaligne, Ronan; Gu, Hongcang
- Nature, Vol. 569, Issue 7757
Fine-Grained Analysis of Spontaneous Mutation Spectrum and Frequency in Arabidopsis thaliana
journal, December 2018
- Weng, Mao-Lun; Becker, Claude; Hildebrandt, Julia
- Genetics, Vol. 211, Issue 2
Somatic mutations substantially increase the per-generation mutation rate in the conifer Picea sitchensis
journal, June 2019
- Hanlon, Vincent C. T.; Otto, Sarah P.; Aitken, Sally N.
- Evolution Letters, Vol. 3, Issue 4
Reduced representation bisulfite sequencing for comparative high-resolution DNA methylation analysis
journal, October 2005
- Meissner, A.
- Nucleic Acids Research, Vol. 33, Issue 18
The Rate and Molecular Spectrum of Spontaneous Mutations in Arabidopsis thaliana
journal, December 2009
- Ossowski, S.; Schneeberger, K.; Lucas-Lledo, J. I.
- Science, Vol. 327, Issue 5961
MethylC-seq library preparation for base-resolution whole-genome bisulfite sequencing
journal, February 2015
- Urich, Mark A.; Nery, Joseph R.; Lister, Ryan
- Nature Protocols, Vol. 10, Issue 3
Spontaneous epigenetic variation in the Arabidopsis thaliana methylome
journal, September 2011
- Becker, Claude; Hagmann, Jörg; Müller, Jonas
- Nature, Vol. 480, Issue 7376
A Role for RNAi in the Selective Correction of DNA Methylation Defects
journal, March 2009
- Teixeira, Felipe Karam; Heredia, Fabiana; Sarazin, Alexis
- Science, Vol. 323, Issue 5921
Establishing, maintaining and modifying DNA methylation patterns in plants and animals
journal, February 2010
- Law, Julie A.; Jacobsen, Steven E.
- Nature Reviews Genetics, Vol. 11, Issue 3
Changes in genomic methylation patterns during the formation of triploid asexual dandelion lineages: EPIGENETIC VARIATION IN ASEXUAL DANDELIONS
journal, December 2009
- Verhoeven, Koen Jf; Van Dijk, Peter J.; Biere, Arjen
- Molecular Ecology, Vol. 19, Issue 2
Sexual-lineage-specific DNA methylation regulates meiosis in Arabidopsis
journal, December 2017
- Walker, James; Gao, Hongbo; Zhang, Jingyi
- Nature Genetics, Vol. 50, Issue 1
Genotype Probabilities at Intermediate Generations in the Construction of Recombinant Inbred Lines
journal, February 2012
- Broman, Karl W.
- Genetics, Vol. 190, Issue 2
Conservation and divergence of methylation patterning in plants and animals
journal, April 2010
- Feng, S.; Cokus, S. J.; Zhang, X.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 19
A genome assembly and the somatic genetic and epigenetic mutation rate in a wild long-lived perennial Populus trichocarpa
journal, October 2020
- Hofmeister, Brigitte T.; Denkena, Johanna; Colomé-Tatché, Maria
- Genome Biology, Vol. 21, Issue 1
Century-scale Methylome Stability in a Recently Diverged Arabidopsis thaliana Lineage
journal, January 2015
- Hagmann, Jörg; Becker, Claude; Müller, Jonas
- PLoS Genetics, Vol. 11, Issue 1
under dependency
journal, August 2001
- Yekutieli, Daniel; Benjamini, Yoav
- The Annals of Statistics, Vol. 29, Issue 4
Rate, spectrum, and evolutionary dynamics of spontaneous epimutations
journal, May 2015
- van der Graaf, Adriaan; Wardenaar, René; Neumann, Drexel A.
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 21
A comparison of single-cell trajectory inference methods
journal, April 2019
- Saelens, Wouter; Cannoodt, Robrecht; Todorov, Helena
- Nature Biotechnology, Vol. 37, Issue 5
Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning
journal, February 2008
- Cokus, Shawn J.; Feng, Suhua; Zhang, Xiaoyu
- Nature, Vol. 452, Issue 7184
Multilocus Patterns of Nucleotide Polymorphism and the Demographic History of Populus tremula
journal, August 2008
- Ingvarsson, Pär K.
- Genetics, Vol. 180, Issue 1
Stress induced gene expression drives transient DNA methylation changes at adjacent repetitive elements
journal, July 2015
- Secco, David; Wang, Chuang; Shou, Huixia
- eLife, Vol. 4
Environmentally responsive genome-wide accumulation of de novo Arabidopsis thaliana mutations and epimutations
journal, October 2014
- Jiang, Caifu; Mithani, Aziz; Belfield, Eric J.
- Genome Research, Vol. 24, Issue 11
The architecture of intra-organism mutation rate variation in plants
journal, April 2019
- Wang, Long; Ji, Yilun; Hu, Yingwen
- PLOS Biology, Vol. 17, Issue 4
Spontaneous epimutations in plants
journal, September 2018
- Johannes, Frank; Schmitz, Robert J.
- New Phytologist, Vol. 221, Issue 3
The evolution of CHROMOMETHYLASES and gene body DNA methylation in plants
journal, May 2017
- Bewick, Adam J.; Niederhuth, Chad E.; Ji, Lexiang
- Genome Biology, Vol. 18, Issue 1
The Arabidopsis DNA Methylome Is Stable under Transgenerational Drought Stress
journal, October 2017
- Ganguly, Diep R.; Crisp, Peter A.; Eichten, Steven R.
- Plant Physiology, Vol. 175, Issue 4
A Robust, Simple Genotyping-by-Sequencing (GBS) Approach for High Diversity Species
journal, May 2011
- Elshire, Robert J.; Glaubitz, Jeffrey C.; Sun, Qi
- PLoS ONE, Vol. 6, Issue 5, Article No. e19379
Quantitative Epigenetics Through Epigenomic Perturbation of Isogenic Lines
journal, May 2011
- Johannes, Frank; Colomé-Tatché, Maria
- Genetics, Vol. 188, Issue 1
Apomixis: Embryo Sacs and Embryos Formed without Meiosis or Fertilization in Ovules
journal, October 1993
- Koltunow, Anna M.
- The Plant Cell, Vol. 5, Issue 10
Highly Integrated Single-Base Resolution Maps of the Epigenome in Arabidopsis
journal, May 2008
- Lister, Ryan; O'Malley, Ronan C.; Tonti-Filippini, Julian
- Cell, Vol. 133, Issue 3
Single-cell expression noise and gene-body methylation in Arabidopsis thaliana
journal, January 2019
- Horvath, Robert; Laenen, Benjamin; Takuno, Shohei
- Heredity, Vol. 123, Issue 2
Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants
journal, September 2011
- Schmitz, R. J.; Schultz, M. D.; Lewsey, M. G.
- Science, Vol. 334, Issue 6054
Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome
journal, June 2015
- Stroud, Hume; Greenberg, Maxim V. C.; Feng, Suhua
- Cell, Vol. 161, Issue 7
Apomixis: Embryo Sacs and Embryos Formed without Meiosis or Fertilization in Ovules.
journal, October 1993
- Koltunow, A. M.
- The Plant Cell