[en] As essential B vitamin for humans, folates accumulation in edible parts of crops, such as maize kernels, is of great importance for human health. But its breeding is always limited by the prohibitive cost of folate profiling. The molecular breeding is a more executable and efficient way for folate fortification, but is limited by the molecular knowledge of folate regulation. Here we report the genetic mapping of folate quantitative trait loci (QTLs) using a segregated population crossed by two maize lines, one high in folate (GEMS31) and the other low in folate (DAN3130). Two folate QTLs on chromosome 5 were obtained by the combination of F2 whole-exome sequencing and F3 kernel-folate profiling. These two QTLs had been confirmed by bulk segregant analysis using F6 pooled DNA and F7 kernel-folate profiling, and were overlapped with QTLs identified by another segregated population. These two QTLs contributed 41.6% of phenotypic variation of 5-formyltetrahydrofolate, the most abundant storage form among folate derivatives in dry maize grains, in the GEMS31×DAN3130 population. Their fine mapping and functional analysis will reveal details of folate metabolism, and provide a basis for marker-assisted breeding aimed at the enrichment of folates in maize kernels.
Disciplines :
Genetics & genetic processes
Author, co-author :
Guo, Wenzhu ✱; College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
Lian, Tong ✱; Université de Liège - ULiège > TERRA Research Centre ; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Wang, Baobao ✱; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Guan, Jiantao ✱; Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Yuan, Dong; Department of Chemistry and Chemical Engineering, Qilu Normal University, Jinan, 250200, China
Wang, Huan; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Safiul Azam, Fardous Mohammad; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Wan, Xing; School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China
Wang, Weixuan; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Liang, Qiuju; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Wang, Haiyang; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Tu, Jinxing; College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
Zhang, Chunyi; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
Jiang, Ling; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
NSCF - National Natural Science Foundation of China [CN]
Funding text :
This work was financially supported by the Ministry of Science and Technology of China (2016YFD0100503 to L.J.), the National Natural Science Foundation of China (31870283 to L.J.), Shanghai Agriculture Applied Technology Development Program (Z20180103 to L.J.), Beijing Natural Science Foundation (6172032 to B.W.).
Abbasi IHR, Abbasi F, Wang L, Abd El Hack ME, Swelum AA, Hao R, Yao J, Cao Y (2018) Folate promotes S-adenosyl methionine reactions and the microbial methylation cycle and boosts ruminants production and reproduction. AMB Exp 8: 65
Bae S, Ulrich CM, Bailey LB, Malysheva O, Brown EC, Maneval DR, Neuhouser ML, Cheng TYD, Miller JW, Zheng YY, Xiao LR, Hou LF, Song XL, Buck K, Beresford SAA, Caudill MA (2014) Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Women's Health Initiative Observational Study cohort. Epigenetics 9: 396–403
Besson V, Rebeille F, Neuburger M, Douce R, Cossins EA (1993) Effects of tetrahydrofolate polyglutamates on the kinetic parameters of serine hydroxymethyltransferase and glycine decarboxylase from pea leaf mitochondria. Biochem J 292: 425–430
Bhutta ZA, Salam RA (2012) Global nutrition epidemiology and trends. Ann Nutr Metab 61: 19–27
Blancquaert D, Storozhenko S, Loizeau K, De Steur H, De Brouwer V, Viaene J, Ravanel S, Rebeille F, Lambert W, Van Der Straeten D (2010) Folates and folic acid: from fundamental research toward sustainable health. Crit Rev Plant Sci 29: 14–35
Blancquaert D, Van Daele J, Strobbe S, Kiekens F, Storozhenko S, De Steur H, Gellynck X, Lambert W, Stove C, Van Der Straeten D (2015) Improving folate (vitamin B-9) stability in biofortified rice through metabolic engineering. Nat Biotechnol 33: 1076–1078
Broman KW, Wu H, Sen S, Churchill GA (2003) R/qtl: QTL mapping in experimental crosses. Bioinformatics 19: 889–890
Chang X, DeFries RS, Liu L, Davis K (2018) Understanding dietary and staple food transitions in China from multiple scales. PLoS ONE 13: e0195775
Chen ZL, Wang BB, Dong XM, Liu H, Ren LH, Chen J, Hauck A, Song WB, Lai JS (2014a) An ultra-high density bin-map for rapid QTL mapping for tassel and ear architecture in a large F-2 maize population. BMC Genomics 15: 433
Chen J, Zeng B, Zhang M, Xie SJ, Wang GK, Hauck A, Lai JS (2014b) Dynamic transcriptome landscape of maize embryo and endosperm development. Plant Physiol 166: 252–264
Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, Snover DC, Church TR, Allen JI, Robertson DJ, Beck GJ, Bond JH, Byers T, Mandel JS, Mott LA, Pearson LH, Barry EL, Rees JR, Marcon N, Saibil F, Ueland PM, Greenberg ER (2007) Folic acid for the prevention of colorectal adenomas: A randomized clinical trial. Jama-J Am Med Assoc 297: 2351–2359
De Lepeleire J, Strobbe S, Verstraete J, Blancquaert D, Ambach L, Visser RGF, Stove C, Van Der Straeten D (2018) Folate biofortification of potato by tuber-specific expression of four folate biosynthesis genes. Mol Plant 11: 175–188
Diaz de la Garza R, Quinlivan EP, Klaus SM, Basset GJ, Gregory JF 3rd, Hanson AD (2004) Folate biofortification in tomatoes by engineering the pteridine branch of folate synthesis. Proc Natl Acad Sci USA 101: 13720–13725
Diaz de la Garza R, Gregory JF 3rd, Hanson AD (2007) Folate biofortification of tomato fruit. Proc Natl Acad Sci USA 104: 4218–4222
Dong W, Cheng Z, Wang X, Wang B, Zhang H, Su N, Yamamaro C, Lei C, Wang J, Wang J, Zhang X, Guo X, Wu F, Zhai H, Wan J (2011) Determination of folate content in rice germplasm (Oryza sativa L.) using tri-enzyme extraction and microbiological assays. Int J Food Sci Nutr 62: 537–543
Ferrer JL, Ravanel S, Robert M, Dumas R (2004) Crystal structures of cobalamin-independent methionine synthase complexed with zinc, homocysteine, and methyltetrahydrofolate. J Biol Chem 279: 44235–44238
Gorelova V, De Lepeleire J, Van Daele J, Pluim D, Mei C, Cuypers A, Leroux O, Rebeille F, Schellens JHM, Blancquaert D, Stove CP, Van Der Straeten D (2017) Dihydrofolate reductase/thymidylate synthase fine-tunes the folate status and controls redox homeostasis in plants. Plant Cell 29: 2831–2853
Guo QN, Wang HD, Tie LZ, Li T, Xiao H, Long JG, Liao SX (2017) Parental genetic variants, MTHFR 677C > T and MTRR 66A>G, associated differently with fetal congenital heart defect. BioMed Res Int 2017: doi: 10.1155/2017/3043476
Hanson AD, Gregory JF 3rd (2011) Folate biosynthesis, turnover, and transport in plants. Annu RevPlant Biol 62: 105–125
Huang X, Feng Q, Qian Q, Zhao Q, Wang L, Wang A, Guan J, Fan D, Weng Q, Huang T, Dong G, Sang T, Han B (2009) High-throughput genotyping by whole-genome resequencing. Genome Res 19: 1068–1076
Jiang L, Wang W, Lian T, Zhang C (2017) Manipulation of metabolic pathways to develop vitamin-enriched crops for human health. Front Plant Sci 8: 937
Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760
Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, Proc GPD (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25: 2078–2079
Li H, Peng Z, Yang X, Wang W, Fu J, Wang J, Han Y, Chai Y, Guo T, Yang N, Liu J, Warburton ML, Cheng Y, Hao X, Zhang P, Zhao J, Liu Y, Wang G, Li J, Yan J (2013) Genome-wide association study dissects the genetic architecture of oil biosynthesis in maize kernels. Nat Genet 45: 43–50
Lian T, Guo WZ, Chen MR, Li JL, Liang QJ, Liu F, Meng HY, Xu BS, Chen JF, Zhang CY, Jiang L (2015) Genome-wide identification and transcriptional analysis of folate metabolism-related genes in maize kernels. BMC Plant Biol 15: 204
Liang QJ, Wang K, Liu XN, Riaz B, Jiang L, Wan X, Ye XG, Zhang CY (2019) Improved folate accumulation in genetically modified maize and wheat. J Exp Bot 70: 1539–1551
Lu XD, Liu JS, Ren W, Yang Q, Chai ZG, Chen RM, Wang L, Zhao J, Lang ZH, Wang HY, Fan YL, Zhao J, Zhang CY (2018) Gene-indexed mutations in maize. Mol Plant 11: 496–504
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA (2010) The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: 1297–1303
Mickelson SM, Stuber CS, Senior L, Kaeppler SM (2002) Quantitative trait loci controlling leaf and tassel traits in a B73 x MO17 population of maize. Crop Sci 42: 1902–1909
Moore EM, Ames D, Mander AG, Carne RP, Brodaty H, Woodward MC, Boundy K, Ellis KA, Bush AI, Faux NG, Martins RN, Masters CL, Rowe CC, Szoeke C, Watters DA (2014) Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: Combined data from three cohorts. J Alzheimers Dis 39: 661–668
Murigneux A, Barloy D, Leroy P, Beckert M (1993) Molecular and morphological evaluation of doubled haploid lines in maize. 1. Homogeneity within DH lines. Theor Appl Genet 86: 837–842
Naqvi S, Zhu C, Farre G, Ramessar K, Bassie L, Breitenbach J, Perez Conesa D, Ros G, Sandmann G, Capell T, Christou P (2009) Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways. Proc Natl Acad Sci USA 106: 7762–7767
Pan QC, Xu YC, Li K, Peng Y, Zhan W, Li WQ, Li L, Yan JB (2017) The genetic basis of plant architecture in 10 maize recombinant inbred line populations. Plant Physiol 175: 858–873
Peiffer JA, Romay MC, Gore MA, Flint-Garcia SA, Zhang ZW, Millard MJ, Gardner CAC, McMullen MD, Holland JB, Bradbury PJ, Buckler ES (2014) The genetic architecture of maize height. Genetics 196: 1337–1356
Pixley K, Warburton M, Xie C (2010) Molecular marker-assisted breeding options for maize improvement in Aisa. Mol Breed 26: 339–356
Price AH (2006) Believe it or not, QTLs are accurate! Trends Plant Sci 11: 213–216
Rader JI, Schneeman BO (2006) Prevalence of neural tube defects, folate status, and folate fortification of enriched cereal-grain products in the United States. Pediatrics 117: 1394–1399
Raihan MS, Liu J, Huang J, Guo H, Pan QC, Yan JB (2016) Multi-environment QTL analysis of grain morphology traits and fine mapping of a kernel-width QTL in Zheng58 x SK maize population. Theor Appl Genet 129: 1465–1477
Robbins ML, Wang PH, Sekhon RS, Chopra S (2009) Gene structure induced epigenetic modifications of pericarp color1 alleles of maize result in tissue-specific mosaicism. PLoS ONE 4: e8231
Sekhon RS, Lin H, Childs KL, Hansey CN, Buell CR, de Leon N, Kaeppler SM (2011) Genome-wide atlas of transcription during maize development. Plant Physiol 66: 553–563
Silva Lda C, Wang S, Zeng ZB (2012) Composite interval mapping and multiple interval mapping: Procedures and guidelines for using Windows QTL Cartographer. Methods Mol Biol 871: 75–119
Silver MJ, Kessler NJ, Hennig BJ, Dominguez-Salas P, Laritsky E, Baker MS, Coarfa C, Hernandez-Vargas H, Castelino JM, Routledge MN, Gong YY, Herceg Z, Lee YS, Lee K, Moore SE, Fulford AJ, Prentice AM, Waterland RA (2015) Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Biol 16: 118
Stelpflug S, Sekhon R, Vaillancourt B, Hirsch C, Buell C, de Leon N, Kaeppler S (2015) An expanded maize gene expression atlas based on RNA sequencing and its use to explore root development. Plant Genome 9: 1
Storozhenko S, De Brouwer V, Volckaert M, Navarrete O, Blancquaert D, Zhang GF, Lambert W, Van Der Straeten D (2007) Folate fortification of rice by metabolic engineering. Nat Biotechnol 25: 1277–1279
Strobbe S, Van Der Straeten D (2017) Folate biofortification in food crops. Curr Opin Biotech 44: 202–211
Suh JR, Herbig AK, Stover PJ (2001) New perspectives on folate catabolism. Annu Rev Nutr 21: 255–282
Takagi H, Abe A, Yoshida K, Kosugi S, Natsume S, Mitsuoka C, Uemura A, Utsushi H, Tamiru M, Takuno S, Innan H, Cano LM, Kamoun S, Terauchi R (2013) QTL-seq: Rapid mapping of quantitative trait loci in rice by whole genome resequencing of DNA from two bulked populations. Plant J 74: 174–183
Vales M, Schön C, Capettini F, Chen X, Corey A, Mather D, Mundt C, Richardson K, Sandoval-Islas J, Utz H, Hayes P (2005) Effect of population size on the estimation of QTL: A test using resistance to barley stripe rust. Theor Appl Genet 111: 1260–1270
Wang BB, Zhu YB, Zhu JJ, Liu ZP, Liu H, Dong XM, Guo JJ, Li W, Chen J, Gao C, Zheng XM, E L, Lai JS, Zhao HM, Song WB (2018) Identification and fine-mapping of a major maize leaf width QTL in a re-sequenced large recombinant inbred lines population. Front Plant Sci 9: 101
Waskiewicz A, Piotrowski W, Broda G, Sobczyk-Kopciol A, Ploski R (2011) Impact of MTHFR C677T gene polymorphism, folate, B6 and B12 vitamin intake on homocysteine concentration in polish adult population. Eur Heart J 32: 720–720
Winter D, Vinegar B, Nahal H, Ammar R, Wilson G, Provart N (2007) An “Electronic Fluorescent Pictograph” browser for exploring and analyzing large-scale biological data sets. PLOS ONE 2: e718
Xu GH, Wang XF, Huang C, Xu DY, Li D, Tian JG, Chen QY, Wang CL, Liang YM, Wu YY, Yang XH, Tian F (2017) Complex genetic architecture underlies maize tassel domestication. New Phytol 214: 852–864
Xu ST, Zhang DL, Cai Y, Zhou Y, Shah T, Ali F, Li Q, Li ZG, Wang WD, Li JS, Yang XH, Yan JB (2012) Dissecting tocopherols content in maize (Zea mays L.), using two segregating populations and high-density single nucleotide polymorphism markers. BMC Plant Biol 12: 201
Yang XH, Gao SB, Xu ST, Zhang ZX, Prasanna BM, Li L, Li JS, Yan JB (2011) Characterization of a global germplasm collection and its potential utilization for analysis of complex quantitative traits in maize. Mol Breed 28: 511–526
Yu HH, Xie WB, Wang J, Xing YZ, Xu CG, Li XH, Xiao JH, Zhang QF (2011) Gains in QTL detection using an ultra-high density SNP map based on population sequencing relative to traditional RFLP/SSR markers. PLoS ONE 6: e17595
Zeng Z (1994) Precision mapping of quantitative trait loci. Genetics 136: 1457–1468
