Journal of Plant Genetics and Crop Research

Journal of Plant Genetics and Crop Research

Journal of Plant Genetics and Crop Research

Current Issue Volume No: 1 Issue No: 1

Review Article Open Access Available online freely Peer Reviewed Citation

Rice Epigenetic Pathways: Great Genetic Variation and Implication for Rapid Rice Breeding

Yuan Li 1,   Erik Persson 2 3  

1 Department of Astronomy and Theoretical Physics

2 Nordic Genetic Resource Center

3 Department of Landscape Architecture, Planning and Management

Abstract

Rice, as one of the most important crops in the world, is facing an ever-accelerating challenge from climate change. Epigenetic modification with its substantially high epimutation rate and the possibility for some epigenetic variation to act as a heritable contributor to crop environmental adaptability may hold great potentials for rapid crop breeding. Epigenetic modification is controlled by epigenetic pathways, and mutations disturbing the epigenetic pathways may lead to significant epigenetic and/or genetic changes. This is especially true for rice, whose genome is rich in epigenetic modifications and transposable elements (TEs) that are generally epigenetically silenced. Here, in this paper, we first reviewed the pathways that establish, maintain and remove rice DNA methylation, which is the most well studied epigenetic marker, as well as the genes that are involved. We then discussed how TEs amplify the phenotypic impact of epigenetic changes that could be a result of epigenetic pathway disturbances. At last, we presented the enormous amount of rice genome data that are publically available, within which great genetic variation in the genes that are involved within the epigenetic pathways is embedded. This genetic variation awaits to be exploited for their potentials in generating a heritable source of variation for rapid environmental adaptation, which may hold tremendous importance for rice breeding in the face of climate change.

Author Contributions
Received 31 Jul 2018; Accepted 30 Aug 2018; Published 06 Sep 2018;

Academic Editor: Mounira Elbaz, Regional Center of Researche on Horticulture and Organic Agriculture (CRRHAB) Chott Mariem, Sousse Tunisia · Horticulture, Tunisia

Checked for plagiarism: Yes

Review by: Single-blind

Copyright ©  2018 Yuan Li, et al.

License
Creative Commons License     This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing interests

The authors have declared that no competing interests exist.

Citation:

Yuan Li, Erik Persson (2018) Rice Epigenetic Pathways: Great Genetic Variation and Implication for Rapid Rice Breeding. Journal of Plant Genetics and Crop Research - 1(1):40-46. https://doi.org/10.14302/issn.2641-9467.jgrc-18-2270

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DOI 10.14302/issn.2641-9467.jgrc-18-2270

Introduction

As one of the most important food crops in the world 1,2, rice (Oryza) is, unfortunately, rather sensitive to climate change, for its yield may be significantly reduced by increasing temperature, by rising sea levels (and the associated salinity intrusion), as well as by flooding and droughts 3. Genetic studies have been making great efforts to improve rice ability to handle environmental stresses 3,4. However, there are still lots to be done, especially when the ever-accelerating climate change is bringing more and more unpredictable and extreme weather.

Epigenetics, the study of chromatin marks that include DNA methylation and histone modification 5, may provide great potentials for crop breeding in a rapidly changing climate, due to the remarkably high epimutation rate 6 and the possibility for some epigenetic variation to be a heritable contributor to crop environmental adaptation 7,8,9. Epigenetic modifications exist ubiquitously in nature, they can regulate gene expression by controlling the accessibility of DNA to transcription machinery, and are therefore vital not only for multicellular organisms’ development 10,11,12, but also for all life’s response to their living environment 2,13,14. Comparing to genetic mutation, epigenetic mutation has been found to occur at a much higher rate (can be orders of magnitude more frequent) 6,15,16, especially under stressful conditions 7,17,18. Many spontaneous or stress-induced epigenetic changes can be heritable across generations 7,19,20,21,22 and some of these heritable epigenetic changes occur in or near genes that are involved in stress-responsive pathways and therefore may help crop handle adverse environmental conditions by assisting the regulation of these stress-responsive genes’ expression 7,8,22.

Epigenetic modification is generated through epigenetic pathways, during which epigenetic modifications get established, maintained and removed 5,14. Therefore, mutations at genes encoding enzymes that are involved in epigenetic pathways will have a good chance to create a genome-wide impact on an organism’s epigenetic profile 23,24,25,26. This impact on epigenetic profile may hold great potential to provide an organism with a heritable source of variation for rapid environmental adaptation. Rice is one of the best crops so far that can be used for exploiting genetic variation within the epigenetic pathways to help improve breeding in the face of climate change for the following reasons: 1) the rice genome is significantly rich in transposable elements (TEs), which can help amplify the phenotypic impact of epigenetic changes 27; 2) rice is the most well studied cereal crop within genomics and epigenetics so far 2, so that the rice epigenetic machinery has been relatively well investigated 5, and 3) there are plenty of rice genome data (>3000) that are publicly available and that can serve as a rich source of genetic variation for exploitation 1,28.

DNA Methylation Pathways in Rice with many involved Genes having been Identified

The epigenetic state of an organism is the outcome of different molecular mechanisms such as DNA methylation, histone modifications and variants, as well as non-coding RNA changes 2,14,26,29. Among these molecular mechanisms, DNA methylation at the 5’ position of cytosine has been most well studied so far especially from the perspective of inheritance mechanism and variation 14,30,31. DNA methylation is established, maintained and removed by a series of pathways 14, and most of the proteins that are involved in these pathways have already been identified for rice 5, which provides a good starting point for exploiting the breeding potential of rice’s epigenetic pathways. The recent progress about DNA methylation pathways in rice has been reviewed by Deng et al. 2016 29 and Lanciano & Mirouze 2017 5, therefore here we will only give a brief summary of it.

Epigenetic pathways are relatively conserved between different plant species 2. As in Arabidopsisthaliana 14 rice de novo establishment of DNA methylation is carried out by the RNA-directed DNA methylation (RdDM) pathway 5. There is also RdDM in animals though with a much less important role 32,33. During RdDM, small interfering RNAs (siRNA) are first produced, via several steps, from the target locus, and they then, with the help of a set of proteins, head to the target locus, where the target locus gets eventually methylated by an enzyme that is called domain rearranged methyltransferase (DRM) 5,14. There are three DRM-encoding genes that have been identified in rice so far, OsDRM2, OsDRM1a and OsDRM1b, with the last two not being expressed 34. RdDM takes on two different forms in plant: canonical and non-canonical. The main difference between these two forms lies in the production of siRNA. Canonical RdDM is a proactive de novo methylation process, during which siRNAs production starts from the transcription of target locus by RNA polymerase IV (POL IV) 5,14. In contrast, the non-canonical RdDM is a rather passive remedial strategy that takes action when regular transcription of the target locus (by POL II) has already occurred, and it is the mRNAs produced via regular transcription that will be processed into siRNA 14,35,36. Apart from OsDRM2, POL IV and POL II that have been mentioned above, there are a bunch of other proteins that have also been identified to be possibly involved within the rice RdDM pathways: OsRDR1, OsRDR2, OsRDR6, OsDCL3a, OsDCL3b, OsAGO4a, OsAGO4b, OsAGO1a, OsAGO1b, OsAGO1c, OsAGO1d, OseIF4A, POL V, WAF1 and OsDCL4 etc. 5.

Different from animals where DNA methylation mainly occurs at the CG dinucleotide sequence context, plant DNA methylation takes place at three different sequence contexts: CG, CHG and CHH (H = A, T or C) 37. Plant DNA methylation can be maintained by different mechanisms depending on the sequence context 14. In rice, CG methylation is mainly maintained by the methyltransferase OsMET1-2, that is a possible ortholog of the mammalian DNMT1 enzyme 5. DNMT1 recognizes hemi-methylated CG during DNA duplication and methylates the unmethylated cytosine in the newly-synthesized daughter DNA strand 38. Apart from OsMET1-2, another methyltransferase, OsMET1-1, has also been identified in rice, and OsMET1-1 may have a minor and/or redundant role in maintaining the CG methylation 5. The maintenance of rice CHG methylation is mostly the responsibility of the plant specific chromomethyltransferase OsCMT3a 5. Another rice chromomethyltransferase, OsCMT3b, is also involved in CHG methylation but with a much smaller role. A third rice chromomethyltransferase (OsCMT2) has also been identified, however the function of OsCMT2 is still unknown 5. Rice CHH methylation is mainly maintained by OsDRM2 39 that is also involved in the RdDM pathways 40. The A. thaliana ortholog of OsDRM2, DRM2, maintains CHH methylation through RdDM at RdDM target regions that include certain transposons and repeat sequences 14. In addition, two rice chromatic remodeling proteins OsDDM1a and OsDDM1b also play roles in maintaining DNA methylation; OsDDM1a/b act at CG and CHG methylation within both euchromatins and heterochromatins, but at CHH methylation of small TEs that are mainly located in euchromatins 39.

DNA methylation could be passively lost due to failure in maintaining it, it could also be actively removed enzymatically 14. Different from DNA methylation reaction that is catalyzed by one single enzyme, active DNA demethylation reaction needs a group of enzymes to catalyze several steps of the reaction: DNA glycosylase, apurinic/apyrimidinic endonuclease, DNA phosphatase and DNA ligase etc., with the first enzyme, glycosylase, being conventionally referred to as DNA demethylase 14. So far, there has been six DNA glycosylases that have been identified in rice: ROS1a, ROS1b, ROS1c, ROS1d, DML3a, and DML3b, with ROS1a being most expressed. In addition, the loss-of-function mutation of ROS1a leads to serious developmental problems 5,29.

The Abundant TEs within the Rice Genome Amplify the “Voice” of DNA Methylation Pathway Disruption

Comparing to A. thaliana, the consequences of DNA methylation pathway disruptions in rice tend to be more serious 5,27,29. For example, functional disruption of OsDRM2 leads to failure of RdDM, resulting in various developmental problems such as complete sterility 34,39, while the loss-of-function mutation of the orthologous gene DRM2 in A. thaliana showed almost no morphological differences from the wild type 41. This different “behavior” of rice from A. thaliana may be due to the much higher levels of DNA methylation and the greater proportion of transposable elements (TEs; generally epigenetically silenced 27,42) in the rice genome 2,27,29,43, as well as the fact that most rice genes have associated TEs 27. For example more than 85% of the African cultivated rice genes have been found to be associated with TEs 44.

Epigenetic modification can regulate gene expression and is therefore able to influence phenotypes 2,14, while the substantial TEs in rice genome act like a “loudspeaker” to amplify the phenotypic impact of epigenetic changes that could be a result of epigenetic pathway disruptions. This is, firstly, because TEs are the major targets of de novo RdDM pathways 33, which may process beyond the targeted TEs and methylate the flanking sequences 42,45,46. The spreading of DNA methylation from gene-associated TEs to gene body and/or regulatory sequences may help regulate the expression of the involved genes 42,47. For example, it has been shown that reducing the expression of the OsDCL3a gene that is involved in RdDM can cause ectopic expression of hundreds of MITE-related genes (MITE is one kind of TEs) in rice 27,48. Therefore, it has been proposed that epigenetic regulation of genes may be originally evolved for silencing invading TEs and virus 42.

Secondly, in rice, under stressful condition, TEs may be released from their epigenetic controls as a result of stress-induced epigenetic changes and become activated 27,49. This process may be facilitated by certain mutations within, or other disruptions of the epigenetic pathways 14,50. For example, an A. thaliana mutant impairing the POL IV enzyme that is important for RdDM showed boosted transposition of one specific TE (ONSEN) in response to heat stress, comparing to the wild-type plant 50. In rice, overexpression of the ROS1c/DNG701 gene that is involved in DNA demethylation caused more frequent transposition of one specific TE (Tos17) in calli (a stress-like condition) 51. The activated TEs transpose from one genomic region to another and this will not only modify genomic sequences and generate genetic diversity 27,49, but also likely bring epigenetic modification to the recipient genomic regions that may establish new TE-associated genes 50.

These TE-induced epigenetic and genetic variation may hold great potentials for creating phenotypic diversity that would contribute to rice environmental adaptability 27. For example, an artificially induced insertion of one specific TE (mping) into the intron of the rice Hd1 gene, which is important for photoperiod sensitivity, has been shown to cause flowering time change, and this may help Nipponbare adapt to different photoperiods; Nipponbare is the temperate japonica rice cultivar that flowers under longer day length than the tropical japonica rice cultivars 27,52.

Over 3000 Rice Genomes as a Rich Resource of Genetic Variation Awaits to be Exploited

From above, we know that disturbance of epigenetic pathways may create both epigenetic and genetic variation, which could modify phenotypes and might therefore help breed for climate changes. Then, where are we going to find genetic variation that can cause such epigenetic pathway disturbance? For the economically very important crop, rice, there is, luckily, a large amount of publically available genome data that we can resort to.

Rice has the smallest genome (ca. 375 mega base pairs 1) among the major cereal crops 52, therefore its genome has been extensively sequenced 44,53,54,55. Especially, the 3000 Rice Genomes Project has acquired the sequences of 3010 Asian cultivated rice (Oryzasativa L) genomes with a global representation of the genetic diversity within this rice species 1,55. Rice is well known for its substantial genetic diversity 56,57,58,59,60,61, for example, a recent analysis of the 3010 rice genomes has revealed 29 million single nucleotide polymorphisms and over 2.4 million indels 1. This enormous amount of genetic variation within the over 3000 rice genomes represents a great starting point for exploring the genes encoding proteins that are involved within the rice DNA methylation pathways in their potentials to influence epigenetic profiles.

Conclusion and Future Perspective

In the agriculturally very important crop, rice, whose genome is rich in epigenetic modifications and TEs 2,27,29,43, epigenetic pathways disturbance may dramatically change the epigenetic profile, and could therefore lead to phenotypic variation 5,27,29. The phenotypic impact of epigenetic changes in rice may be significantly amplified by TEs via creating both epigenetic and genetic variation 27,42,45,46,49. Now many genes involved in the pathways of establishing, maintaining and removing DNA methylation, which is the most well studied epigenetic marker so far, have been identified 2,5. The genetic variation of these genes that are embedded within the over 3000 publically available rice genomes 55 awaits to be exploited in their potential to generate a heritable source of variation for the rapid adaptation of rice, which may hold tremendous importance for rice breeding that is facing an increasing challenge from climate change.

Considering the likely large amount of genetic variation at genes that are embedded within the over 3000 rice genomes, it would be time- and labor-consuming to experimentally examine each of the genetic variants. Therefore, a preliminary selection by, for example, predicting the possible influences of these genetic variants on the function, activity, stability, etc., of the involved proteins would be a smart starting point.

Acknowledgements

Yuan Li would like to thank financial support from Stiftelsen Olle ENGKVIST Byggmästare.

References

  1. 1.Wang W, Mauleon R, Hu Z, Chebotarov D, Tai.Set al.(2018) Genomic variation in 3,010 diverse accessions of Asian cultivated rice. , Nature 557(7703), 43-49.
  1. 2.Chen X, Zhou D-X. (2013) Rice epigenomics and epigenetics: challenges and opportunities. , Curr. Opin. Plant Biol 16(2), 164-169.
  1. 3.Jagadish SVK, Septiningsih E M, Kohli A, Thomson M J, Ye.Cet al.(2012) Genetic advances in adapting rice to a rapidly changing climate. , J. Agron. Crop. Sci 198(5), 360-373.
  1. 4.Jez J M, Lee S G, Sherp A M. (2016) The next green movement: plant biology for the environment and sustainability. , Science 353(6305), 1241-1244.
  1. 5.Lanciano S, Mirouze M. (2017) DNA methylation in rice and relevance for breeding. , Epigenomes 1(2), 10.
  1. 6.Graaf A Van Der, Wardenaar R, Neumann D A, Taudt A, Shaw.RGet al.(2015) Rate, spectrum, and evolutionary dynamics of spontaneous epimutations. , Proc. Natl. Acad. Sci. USA 112(21), 6676-6681.
  1. 7.Zheng X, Chen L, Xia H, Wei H, Lou.Qet al.(2017) Transgenerational epimutations induced by multi-generation drought imposition mediate rice plant’s adaptation to drought condition. , Sci. Rep 7, 39843.
  1. 8.Paul A, Dasgupta P, Roy D, Chaudhuri S. (2017) . Comparative analysis of Histone modifications and DNA methylation atOsBZ8locus under salinity stress in IR64 and Nonabokra rice varieties.PlantMol.Biol;95(1-2) 63-88.
  1. 9.Xia H, Huang W X, Xiong J, Tao T, Zheng.XGet al.(2016) Adaptive epigenetic differentiation between upland and lowland rice ecotypes revealed by methylation-sensitive amplified polymorphism. , PLoS One 11(7), 0157810.
  1. 10.Alberts B, Johnson A D, Lewis J, Raff M, Roberts.. Ket al.(2002) Molecular Biology of the Cell, 5th Ed , Garland Science, New York .
  1. 11.Zhang M, Kimatu J N, Xu K, Liu B. (2010) DNA cytosine methylation in plant development. , J. Genet. Genomics 37(1), 1-12.
  1. 12.Smith Z D, Meissner A. (2013) DNA methylation: roles in mammalian development. , Nat. Rev. Genet 14(3), 204-220.
  1. 13.Duncan E J, Gluckman P D, Dearden P K. (2014) Epigenetics, plasticity, and evolution: How do we link epigenetic change to phenotype?. , J. Exp. Zool. (Mol. Dev. Evol.);322B(4) 208-220.
  1. 14.Zhang H, Lang Z, Zhu J-K. (2018) Dynamics and function of DNA methylation in plants. , Nat. Rev. Mol. Cell. Biol 19(8), 489-506.
  1. 15.Becker C, Hagmann J, Müller J, Koenig D, Stegle.Oet al.(2011) Spontaneous epigenetic variation in theArabidopsis thalianamethylome. , Nature 480(7376), 245-249.
  1. 16.Schmitz R J, Schultz M D, Lewsey M G, O’Malley R C.Urich MAet al.(2011) Transgenerational epigenetic instability is a source of novel methylation variants. , Science 334(6054), 369-373.
  1. 17.Dowen R H, Pelizzola M, Schmitz R J, Lister R, Dowen.JMet al.(2012) Widespread dynamic DNA methylation in response to biotic stress. , Proc. Natl. Acad. Sci. USA 109(32), 2183-2191.
  1. 18.Ong-Abdullah M, Ordway J M, Jiang N, Ooi S-E, Kok.S-Yet al.(2015) Loss ofKarmatransposon methylation underlies the mantled somaclonal variant of oil palm. , Nature 525(7570), 533-537.
  1. 19.Martienssen R A, Colot V. (2001) DNA methylation and epigenetic inheritance in plants and filamentous fungi. , Science 293(5532), 1070-1074.
  1. 20.Quadrana L, Colot V. (2016) Plant transgenerational epigenetics. , Annu. Rev. Genet 50(1), 467-491.
  1. 21.Ou X F, Zhang Y H, Xu C M, Lin X Y, Zang.Qet al.(2012) Transgenerational inheritance of modified DNA methylation patterns and enhanced tolerance induced by heavy metal stress in rice (Oryza sativaL.). , PLoS One 7(9), 41143.
  1. 22.Zheng X G, Chen L, Li M S, Lou Q J, Xia.Het al.(2013) Transgenerational variations in DNA methylation induced by drought stress in two rice varieties with distinguished difference to drought resistance. , PLoS One 8(11), 80253.
  1. 23.Yamauchi T, Johzuka-Hisatomi Y, Terada R, Nakamura I, Iida S. (2014) TheMET1bgene encoding a maintenance DNA methyltransferase is indispensable for normal development in rice. , Plant Mol. Biol 85(3), 219-232.
  1. 24.Hu L, Li N, Xu C, Zhong S, Lin.Xet al.(2014) Mutation of a major CG methylase in rice causes genome-wide hypomethylation, dysregulated genome expression, and seedling lethality. , Proc. Natl. Acad. Sci. USA 111(29), 10642-10647.
  1. 25.Anderson S N, Zynda G, Song J, Han Z, Vaughn.Met al.(2018) Subtle perturbations of the maize methylome reveal genes and transposons silenced by chromomethylase or RNA-directed DNA methylation pathways. G3–Genes Genom. , Genet 8(6), 1921-1932.
  1. 26.Taudt A, Colomé-Tatché M, Johannes F. (2016) Genetic sources of population epigenomic variation. , Nat. Rev. Genet 17(6), 319-332.
  1. 27.Song X, Cao X. (2017) Transposon-mediated epigenetic regulation contributes to phenotypic diversity and environmental adaptation in rice. , Curr. Opin. Plant Biol 36, 111-118.
  1. 28.Li J-Y, Wang J, Zeigler R S. (2014) The 3,000 rice genomes project: new opportunities and challenges for future rice research. GigaScience;3(1),8
  1. 29.Deng X, Song X, Wei L, Liu C, Cao X. (2016) Epigenetic regulation and epigenomic landscape in rice. , Natl. Sci. Rev 3(3), 309-327.
  1. 30.Teschendorff A E, Relton C L. (2018) Statistical and integrative system-level analysis of DNA methylation data. , Nat. Rev. Genet 19(3), 129-147.
  1. 31.Springer N M, Schmitz R J. (2017) Exploiting induced and natural epigenetic variation for crop improvement. , Nat. Rev. Genet 18(9), 563-575.
  1. 32.Watanabe T, Tomizawa S-i, Mitsuya K, Totoki Y, Yamamoto.Yet al.(2011) Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouseRasgrf1locus. , Science 332(6031), 848-852.
  1. 33.Matzke M A, Mosher R A. (2014) RNA-directed DNA methylation: an epigenetic pathway of increasing complexity. , Nat. Rev. Genet 15(6), 394-408.
  1. 34.Moritoh S, Eun C H, Ono A, Asao H, Okano.Yet al.(2012) Targeted disruption of an orthologue of DOMAINS REARRANGED METHYLASE 2, OsDRM2, impairs the growth of rice plants by abnormal DNA methylation. , Plant J 71(1), 85-98.
  1. 35.Wendte J M, Pikaard C S. (2017) The RNAs of RNA-directed DNA methylation. , Biochim. Biophys. Acta 1860(1), 140-148.
  1. 36.Cuerda-Gil D, Slotkin R K. (2016) Non-canonical RNA-directed DNA methylation. , Nat. Plants 2(11), 16163.
  1. 37.Du J, Johnson L M, Jacobsen S E, Patel D J. (2015) DNA methylation pathways and their crosstalk with histone methylation. , Nat. Rev. Mol. Cell. Biol 16(9), 519-532.
  1. 38.He X-J, Chen T, Zhu J-K. (2011) Regulation and function of DNA methylation in plants and animals. Cell Res. 21(3), 442-465.
  1. 39.Tan F, Zhou C, Zhou Q, Zhou S, Yang.Wet al.(2016) Analysis of chromatin regulators reveals specific features of rice DNA methylation pathways. Plant Physiol. 171(3), 2041-2054.
  1. 40.Pang J, Dong M, Li N, Zhao Y, Liu B. (2013) Functional characterization of a rice de novo DNA methyltransferase, OsDRM2, expressed inEscherichia coliand yeast. , Biochem. Biophys. Res. Commun 432(1), 157-162.
  1. 41.Cao X, Jacobsen S E. (2002) Role of theArabidopsisDRM methyltransferases in de novo DNA methylation and gene silencing. , Curr. Biol 12(13), 1138-1144.
  1. 42.Bennetzen J L, Wang H. (2014) The contributions of transposable elements to the structure, function, and evolution of plant genomes. , Annu. Rev. Plant Biol 65(1), 505-530.
  1. 43.Li X, Zhu J, Hu F, Ge S, Ye.Met al.(2012) Single-base resolution maps of cultivated and wild rice methylomes and regulatory roles of DNA methylation in plant gene expression. , BMC Genomics 13(1), 300.
  1. 44.Wang M, Yu Y, Haberer G, Marri P R, Fan.Cet al.(2014) The genome sequence of African rice (Oryzaglaberrima) and evidence for independent domestication. , Nat. Genet 46(9), 982-988.
  1. 45.Hollister J D, Gaut B S. (2009) Epigenetic silencing of transposable elements: a trade-off between reduced transposition and deleterious effects on neighboring gene expression. Genome Res. 19(8), 1419-1428.
  1. 46.Ahmed I, Sarazin A, Bowler C, Colot V, Quesneville H. (2011) Genome-wide evidence for local DNA methylation spreading from small RNA-targeted sequences inArabidopsis. , Nucleic Acids Res 39(16), 6919-6931.
  1. 47.Vidalis A, Živković D, Wardenaar R, Roquis D, Tellier.Aet al.(2016) Methylome evolution in plants. , Genome Biol 17(1), 264.
  1. 48.Wei L, Gu L, Song X, Cui X, Lu.Zet al.(2014) Dicer-like 3 produces transposable element-associated 24-nt siRNAs that control agricultural traits in rice. , Proc. Natl. Acad. Sci. USA 111(10), 3877-3882.
  1. 49.Jiang N, Panaud O. (2013) Transposable element dynamics in rice and its wild relatives. in:Genetics and Genomics ofRice,Springer Science+Business Media. , New York
  1. 50.Ito H, Gaubert H, Bucher E, Mirouze M, Vaillant.Iet al.(2011) An siRNA pathway prevents transgenerational retrotransposition in plants subjected to stress. , Nature 472(7341), 115-119.
  1. 51.La H, Ding B, Mishra G P, Zhou B, Yang.Het al.(2011) A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17 and promotes its transposition in rice. , Proc. Natl. Acad. Sci. USA 108(37), 15498-15503.
  1. 52.Jiang N, Bao Z, Zhang X, Hirochika H, Eddy.SRet al.(2003) An active DNA transposon family in rice. , Nature 421(6919), 163-167.
  1. 53. (2005) International Rice Genome Sequencing Project. The map-based sequence of the rice genome. , Nature 436(7052), 793-800.
  1. 54.Stein J C, Yu Y, Copetti D, Zwickl D J, Zhang.Let al.(2018) Genomes of 13 domesticated and wild rice relatives highlight genetic conservation, turnover and innovation across the genusOryza. , Nat. Genet 50(2), 285-296.
  1. 55. (2014) The 3000 Rice Genomes Project. The 3,000 rice genomes project. , GigaScience 3(1), 7.
  1. 56.Garris A, Tai T H, Coburn J, Kresovich S, McCouch S. (2005) Genetic structure and diversity inOryza sativaL. , Genetics 169(3), 1631-1638.
  1. 57.Han B, Xue Y. (2003) Genome-wide intraspecific DNA-sequence variations in rice. , Curr. Opin. Plant Biol 6(2), 134-138.
  1. 58.Agrama H A, Yan W, Jia M, Fjellstrom R, McClung A M. (2010) Genetic structure associated with diversity and geographic distribution in the USDA rice world collection. , Nat. Sci 2(4), 247-291.
  1. 59.Xu X, Liu X, Ge S, Jensen J D, Hu.Fet al.(2012) Resequencing 50 accessions of cultivated and wild rice yields markers for identifying agronomically important genes. , Nat. Biotechnol 30(1), 105-111.
  1. 60.Zhang J, Chen L-L, Xing F, Kudrna D A, Yao.Wet al.(2016) Extensive sequence divergence between the reference genomes of two eliteindicarice varieties Zhenshan 97 and Minghui 63. , Proc. Natl. Acad. Sci. USA 113(35), 5163-5171.
  1. 61.Alexandrov N, Tai S, Wang W, Mansueto L, Palis.Ket al.(2014) SNP-Seek database of SNPs derived from 3000 rice genomes. , Nucleic Acids Res 43, 1023-1027.