Dissection of genotype-phenotype associations in rice grains using metabolome quantitative trait loci analysis.

A comprehensive and large-scale metabolome quantitative trait loci (mQTL) analysis was performed to investigate the genetic backgrounds associated with metabolic phenotypes in rice grains. The metabolome dataset consisted of 759 metabolite signals obtained from the grains of 85 lines of rice (Oryza sativa, Sasanishiki × Habataki back-crossed inbred lines). Metabolome analysis was performed using four mass spectrometry pipelines to enhance detection of different classes of metabolites. This mQTL analysis of a wide range of metabolites highlighted an uneven distribution of 802 mQTLs on the rice genome, as well as different modes of metabolic trait (m-trait) control among various types of metabolites. The levels of most metabolites within rice grains were highly sensitive to environmental factors, but only weakly associated with mQTLs. Coordinated control was observed for several groups of metabolites, such as amino acids linked to the mQTL hotspot on chromosome 3. For flavonoids, m-trait variation among the experimental lines was tightly governed by genetic factors that alter the glycosylation of flavones. Many loci affecting levels of metabolites were detected by QTL analysis, and plausible gene candidates were evaluated by in silico analysis. Several mQTLs profoundly influenced metabolite levels, providing insight into the control of rice metabolism. The genomic region and genes potentially responsible for the biosynthesis of apigenin-6,8-di-C-α-l-arabinoside are presented as an example of a critical mQTL identified by the analysis.

[1]  Akira Oikawa,et al.  Exploring molecular backgrounds of quality traits in rice by predictive models based on high-coverage metabolomics , 2011, BMC Systems Biology.

[2]  Yuji Sawada,et al.  Mass Spectra-Based Framework for Automated Structural Elucidation of Metabolome Data to Explore Phytochemical Diversity , 2011, Front. Plant Sci..

[3]  Akira Oikawa,et al.  Metabolomics of a Single Vacuole Reveals Metabolic Dynamism in an Alga Chara australis1[W][OA] , 2011, Plant Physiology.

[4]  Rachel E. Kerwin,et al.  Network Quantitative Trait Loci Mapping of Circadian Clock Outputs Identifies Metabolic Pathway-to-Clock Linkages in Arabidopsis[C][W] , 2011, Plant Cell.

[5]  M. Yano,et al.  Discovery of Genome-Wide DNA Polymorphisms in a Landrace Cultivar of Japonica Rice by Whole-Genome Sequencing , 2011, Plant & cell physiology.

[6]  Tadashi Hirasawa,et al.  New approach for rice improvement using a pleiotropic QTL gene for lodging resistance and yield , 2010, Nature communications.

[7]  D. Kliebenstein,et al.  The Complex Genetic Architecture of the Metabolome , 2010, PLoS genetics.

[8]  I. Chu,et al.  CYP93G2 Is a Flavanone 2-Hydroxylase Required for C-Glycosylflavone Biosynthesis in Rice1[W] , 2010, Plant Physiology.

[9]  Kazuki Saito,et al.  Metabolomics for functional genomics, systems biology, and biotechnology. , 2010, Annual review of plant biology.

[10]  W. Friedt,et al.  Genetic mapping of QTLs for sugar-related traits in a RIL population of Sorghum bicolor L. Moench , 2010, Theoretical and Applied Genetics.

[11]  M. Matsuoka,et al.  Gain of deleterious function causes an autoimmune response and Bateson–Dobzhansky–Muller incompatibility in rice , 2010, Molecular Genetics and Genomics.

[12]  M. Yano,et al.  A major quantitative trait locus for increasing cadmium-specific concentration in rice grain is located on the short arm of chromosome 7 , 2009, Journal of experimental botany.

[13]  M. Hirai,et al.  AtMetExpress Development: A Phytochemical Atlas of Arabidopsis Development[W][OA] , 2009, Plant Physiology.

[14]  Joachim Selbig,et al.  Identification of heterotic metabolite QTL in Arabidopsis thaliana RIL and IL populations. , 2009, The Plant journal : for cell and molecular biology.

[15]  M. Fitzgerald,et al.  The origin and evolution of fragrance in rice (Oryza sativa L.) , 2009, Proceedings of the National Academy of Sciences.

[16]  A. Kondo,et al.  Overproduction of Geranylgeraniol by Metabolically Engineered Saccharomyces cerevisiae , 2009, Applied and Environmental Microbiology.

[17]  D. Kliebenstein.  Advancing Genetic Theory and Application by Metabolic Quantitative Trait Loci Analysis , 2009, The Plant Cell Online.

[18]  H. Puschmann,et al.  The C-Glycosylation of Flavonoids in Cereals*♦ , 2009, The Journal of Biological Chemistry.

[19]  A. Korol,et al.  Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat × wild emmer wheat RIL population , 2009, Theoretical and Applied Genetics.

[20]  A. Lommen.  MetAlign: interface-driven, versatile metabolomics tool for hyphenated full-scan mass spectrometry data preprocessing. , 2009, Analytical chemistry.

[21]  M. Fitzgerald,et al.  Not just a grain of rice: the quest for quality. , 2009, Trends in plant science.

[22]  M. Hirai,et al.  A Chloroplastic UDP-Glucose Pyrophosphorylase from Arabidopsis Is the Committed Enzyme for the First Step of Sulfolipid Biosynthesis[W][OA] , 2009, The Plant Cell Online.

[23]  Jingyuan Fu,et al.  System-wide molecular evidence for phenotypic buffering in Arabidopsis , 2009, Nature Genetics.

[24]  Detlef Weigel,et al.  Next-generation genetics in plants , 2008, Nature.

[25]  Kazuo Shinozaki,et al.  MS/MS spectral tag-based annotation of non-targeted profile of plant secondary metabolites , 2008, The Plant journal : for cell and molecular biology.

[26]  W. Sakamoto,et al.  Functional characterization of key structural genes in rice flavonoid biosynthesis , 2008, Planta.

[27]  Bjarne Gram Hansen,et al.  Biochemical Networks and Epistasis Shape the Arabidopsis thaliana Metabolome[W] , 2008, The Plant Cell Online.

[28]  W. G. Hill,et al.  Heritability in the genomics era — concepts and misconceptions , 2008, Nature Reviews Genetics.

[29]  J. Selbig,et al.  Mode of Inheritance of Primary Metabolic Traits in Tomato[W][OA] , 2008, The Plant Cell Online.

[30]  M. Yano,et al.  Genetic dissection and pyramiding of quantitative traits for panicle architecture by using chromosomal segment substitution lines in rice , 2008, Theoretical and Applied Genetics.

[31]  O. Fiehn,et al.  Identification of metabolic and biomass QTL in Arabidopsis thaliana in a parallel analysis of RIL and IL populations , 2007, The Plant journal : for cell and molecular biology.

[32]  Makoto Kobayashi,et al.  Unbiased characterization of genotype-dependent metabolic regulations by metabolomic approach in Arabidopsis thaliana , 2007, BMC Systems Biology.

[33]  Robert D Hall,et al.  Plant metabolomics and its potential application for human nutrition. , 2007, Physiologia plantarum.

[34]  Lincoln Stein,et al.  Gramene: a growing plant comparative genomics resource , 2007, Nucleic Acids Res..

[35]  M. Whitecross,et al.  Isovitexin‐2″‐O‐β‐[6‐O‐E‐p‐coumaroylglucopyranoside] from UV‐B irradiated Leaves of Rice, Oryza sativa L. Inhibits Fertility of Helicoverpa armigera , 2007, Photochemistry and photobiology.

[36]  F. Tomás-Barberán,et al.  Characterization of C-glycosyl flavones O-glycosylated by liquid chromatography-tandem mass spectrometry. , 2007, Journal of chromatography. A.

[37]  Kazuki Saito,et al.  Application of a metabolomic method combining one-dimensional and two-dimensional gas chromatography-time-of-flight/mass spectrometry to metabolic phenotyping of natural variants in rice. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[38]  M. Yano,et al.  Identification and linkage mapping of complementary recessive genes causing hybrid breakdown in an intraspecific rice cross , 2007, Theoretical and Applied Genetics.

[39]  Wei Huang,et al.  A QTL for rice grain width and weight encodes a previously unknown RING-type E3 ubiquitin ligase , 2007, Nature Genetics.

[40]  J. Keurentjes,et al.  Untargeted large-scale plant metabolomics using liquid chromatography coupled to mass spectrometry , 2007, Nature Protocols.

[41]  Kanako O. Koyanagi,et al.  Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana. , 2007, Genome research.

[42]  Oliver Fiehn,et al.  Applications of metabolomics in agriculture. , 2006, Journal of agricultural and food chemistry.

[43]  Jingyuan Fu,et al.  The genetics of plant metabolism , 2006, Nature Genetics.

[44]  U. Roessner,et al.  Comprehensive metabolic profiling and phenotyping of interspecific introgression lines for tomato improvement , 2006, Nature Biotechnology.

[45]  A. Gescher,et al.  The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in ApcMin mice , 2005, Molecular Cancer Therapeutics.

[46]  Takuji Sasaki,et al.  The map-based sequence of the rice genome , 2005, Nature.

[47]  Yu-Chih Liang,et al.  Isovitexin suppresses lipopolysaccharide-mediated inducible nitric oxide synthase through inhibition of NF-kappa B in mouse macrophages. , 2005, Planta medica.

[48]  B. Chiang,et al.  Inhibitory Effects of a Rice Hull Constituent on Tumor Necrosis Factor α, Prostaglandin E2, and Cyclooxygenase‐2 Production in Lipopolysaccharide‐Activated Mouse Macrophages , 2005, Annals of the New York Academy of Sciences.

[49]  Shi-hua Cheng,et al.  Structure, Evolution, and Expression of the Two Invertase Gene Families of Rice , 2005, Journal of Molecular Evolution.

[50]  J. Slate,et al.  INVITED REVIEW: Quantitative trait locus mapping in natural populations: progress, caveats and future directions , 2004, Molecular ecology.

[51]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[52]  N. Syed,et al.  Genetics of quantitative traits in Arabidopsis thaliana , 2003, Heredity.

[53]  M. Morgante,et al.  From plant genomics to breeding practice. , 2003, Current opinion in biotechnology.

[54]  Y. Fukuta,et al.  Quantitative Trait Loci for Sink Size and Ripening Traits in Rice (Oryza sativa L.) , 2002 .

[55]  T. Terao,et al.  Quantitative Trait Loci for Nonstructural Carbohydrate Accumulation in Leaf Sheaths and Culms of Rice (Oryza sativa L.) and their Effects on Grain Filling , 2002 .

[56]  T. Yamaya,et al.  Organ and cellular localization of asparagine synthetase in rice plants. , 2000, Plant & cell physiology.

[57]  Rikke Nørbæk,et al.  Identification of flavone C-glycosides including a new flavonoid chromophore from barley leaves (Hordeum vulgare L.) by improved NMR techniques. , 2000, Journal of agricultural and food chemistry.

[58]  R W Doerge,et al.  Accounting for Variability in the Use of Permutation Testing to Detect Quantitative Trait Loci , 2000, Biometrics.

[59]  M. Horiike,et al.  Isolation and Identification of the Probing Stimulants in the Rice Plant for the White-back Planthopper, Sogatella furcifera (Homoptera: Delphacidae) , 2000, Bioscience, biotechnology, and biochemistry.

[60]  M. Kearsey,et al.  QTL analysis in plants; where are we now? , 1998, Heredity.

[61]  Z B Zeng,et al.  Multiple trait analysis of genetic mapping for quantitative trait loci. , 1995, Genetics.

[62]  R. Doerge,et al.  Empirical threshold values for quantitative trait mapping. , 1994, Genetics.

[63]  R. Mues,et al.  Flavone di-C-glycosides from Plagiochila jamesonii and Plagiochasma rupestre☆ , 1993 .

[64]  G. Franz,et al.  Isolation and Some Properties of an UDP-Glucose: 2-Hydroxyflavanone-6(or 8)-C-Glucosyltransferase from Fagopyrum esculentum M. Cotyledons , 1988 .

[65]  K. R. Markham,et al.  NMR Spectra of Flavone Di-C-glycosides from Apometzgeria pubescens and the Detection of Rotational Isomerism in 8-C-Hexosylflavones , 1987 .

[66]  A. Fernie,et al.  Metabolomics-assisted breeding: a viable option for crop improvement? , 2009, Trends in genetics : TIG.

[67]  T. Kubo,et al.  Epistasis underlying female sterility detected in hybrid breakdown in a Japonica–Indica cross of rice (Oryza sativa L.) , 2004, Theoretical and Applied Genetics.

[68]  K. R. Markham,et al.  C-glycosylflavones from Oryza sativa , 1985 .