The rapid progress in sequencing plant genomes and genes has exposed the lack of inform¬ation regarding the function of >70% of the proteins encoded. In addition, these studies have shown that many such unknowns also occur in bacteria and archaea. Comparative genomics is a powerful approach to uncover gene function, as is advanced in silico reconstruction of an organism's metabolism. In this project, both approaches are used to improve the accuracy of functions assigned to maize metabolic genes and to predict functions for unknown genes, with special emphasis on B vitamins (folate, niacin, thiamin, pyridoxine, riboflavin, pantothenate, and biotin). The most promising functional predictions are experimentally validated by combining genetic and metabolic profiling approaches in bacteria with biochemical assays of recombinant proteins and with genetic tests in maize. The expected overall outcome of this project is the implementation of a comparative genomics prediction and validation pipeline for maize gene function discovery, using B vitamin metabolism as a paradigm. Gene functions (annotations) are publicly available via the PlantSEED websites below.
The project is implementing an interdisciplinary approach to gene function discovery that is extendable to any metabolic network. In the process, it is enriching the maize genome by imposing consistency on thousands of metabolic gene annotations, and by improving the annotations of hundreds of unknown genes. Both impacts advance future function discovery. Furthermore, by developing genome-scale in silico metabolic reconstructions, the work is initiating a systems approach to understanding maize metabolism. Integrally, the work is providing cross-disciplinary training in comparative genomics, metabolic biochemistry, and microbial genetics to students, postdoctoral associates, and faculty. In addition the project holds an annual 3-day hands-on workshop at University of Florida to train researchers to predict functions using the SEED, PlantSEED, and other comparative genomics databases, with special emphasis on training faculty from minority serving institutions. Finally the project contributes to an undergraduate bioinformatics course in which students participate in gene function discovery and metabolic reconstructions using comparative genomics, and to a graduate course in which students develop functional predictions for unknowns in the project.
- Andrew Hanson (Principal Investigator)
- Jesse Gregory (Co-Principal Investigator)
- Donald McCarty (Co-Principal Investigator)
- Valérie de Crécy-Lagard (Co-Principal Investigator)
- Christopher Henry (Co-Principal Investigator)
- Supported by the NSF - NSF Grant No. IOS-1025398
Gene annotation of maize B-vitamin and other metabolic pathways.
- Seaver SM, Gerdes S, Frelin O, Lerma-Ortiz C, Bradbury LM, Zallot R, Hasnain G, Niehaus TD, El Yacoubi B, Pasternak S, Olson R, Pusch G, Overbeek R, Stevens R, de Crécy-Lagard V, Ware D, Hanson AD, Henry CS (2014) High-throughput comparison, functional annotation, and metabolic modeling of plant genomes using the PlantSEED resource. Proc. Nat. Acad. Sci. USA 111: 9645-9650 DOI: 10.1073/pnas.1401329111
- Niehaus TD, Richardson LG, Gidda SK, ElBadawi-Sidhu M, Meissen JK, Mullen RT, Fiehn O, Hanson AD (2014) Plants utilize a highly conserved system for repair of NADH and NADPH hydrates. Plant Physiol. 165: 52-61 DOI: 10.1104/pp.114.236539
- *Zallot R, Yazdani M, Goyer A, Ziemak MJ, Guan J-C, McCarty DR, de Crécy-Lagard V, Gerdes S, Shintani DK, Hanson AD (2014) Salvage of the thiamin pyrimidine moiety by plant TenA proteins lacking an active-site cysteine. Biochem. J. 463: 145-155 DOI: 10.1042/BJ20140522
- Zallot R, Brochier-Armanet C, Gaston KW, Forouhar F, Limbach PA, Hunt JF, de Crécy-Lagard V (2014) Plant, animal, and fungal micronutrient queuosine is salvaged by members of the DUF2419 protein family. ACS Chem. Biol. 9: 1812-1825 DOI: 10.1021/cb500278k
- El Yacoubi B, de Crecy-Lagard V. Integrative data-mining tools to link gene and function. In "Integrative data-mining tools to link gene and function" Ochs MF (ed.), Methods in Molecular Biology: Gene Function Analysis, 2nd Ed., pp. 43-66. Springer, New York, 2014 DOI: 10.1007/978-1-62703-721-1_4
- *Niehaus TD, Nguyen TND, Gidda SK, ElBadawi-Sidhu M, Lambrecht JA, McCarty DR, Downs DM, Cooper AJL, Fiehn O, Mullen RT, Hanson AD (2014) RidA proteins pre-empt reactive imine damage to branched-chain amino acid synthesis in plastids. Plant Cell 26: 3010-3022 DOI: 10.1105/tpc.114.126854
- Guan JC, Hasnain G, Garrett TJ,Chase CD, Gregory J, Hanson AD, McCarty DR (2014) Divisions of labor in the thiamin biosynthetic pathway among tissues of maize. Front. Plant Sci. 5: 370 DOI: 10.3389/fpls.2014.00370
- Hasnain G, Roje S, Frelin O, Ellens KW, Ali K, Guan J-C, Garrett TJ, de Crecy-Lagard V, Gregory JF 3rd, McCarty DR, Hanson AD (2013) Identification and characterization of the missing pyrimidine reductase in the plant riboflavin biosynthesis pathway. Plant Physiol. 161: 48-56 DOI: 10.1104/pp.112.208488.
- *Goyer A, Hasnain G, Frelin O, Ralat MA, Gregory JF, Hanson AD (2013) A cross-kingdom Nudix enzyme that pre-empts damage in thiamin metabolism. Biochem. J. 2013 454: 533-542 DOI: 10.1042/BJ20130516
- Yazdani M, Zallot R, Tunc-Ozdemir M, de Crécy-Lagard V, Shintani DK, Hanson AD (2013) Identification of the thiamin salvage enzyme thiazole kinase in Arabidopsis and maize. Phytochemistry 94: 68-73 DOI: 10.1016/j.phytochem.2013.05.017
- Zallot R, Agrimi G, Lerma-Ortiz C, Teresinski HJ, Frelin O, Ellens KW, Castegna A, Russo A, de Crécy-Lagard V, Mullen RT, Palmieri F, Hanson AD (2013) Identification of mitochondrial coenzyme A transporters from maize and Arabidopsis. Plant Physiol. 162: 581-588 DOI: 10.1104/pp.113.218081
- Seaver SM, Henry CS, Hanson AD (2012) Frontiers in metabolic reconstruction and modeling of plant genomes. J. Exp. Bot. 63: 2247-2258 DOI: 10.1093/jxb/err371
- Jeanguenin L, Lara-Núñez A, Rodionov DA, Osterman AL, Komarova NY, Rentsch D, Gregory JF 3rd, Hanson AD (2012) Comparative genomics and functional analysis of the NiaP family uncover nicotinate transporters from bacteria, plants, and mammals. Funct. Integr. Genomics 12: 25-34 DOI: 10.1007/s10142-011-0255-y
- Frelin O, Agrimi G, Laera VL, Castegna A, Richardson LG, Mullen RT, Lerma-Ortiz C, Palmieri F, Hanson AD (2012) Identification of mitochondrial thiamin diphosphate carriers from Arabidopsis and maize. Funct. Integr. Genomics 12: 317-332 DOI: 10.1007/s10142-012-0273-4
- Gerdes S, Lerma-Ortiz C, Frelin O, Seaver SM, Henry CS, de Crécy-Lagard V, Hanson AD (2012) Plant B vitamin pathways and their compartmentation: a guide for the perplexed. J. Exp. Bot. 63: 5379-5395 DOI: 10.1093/jxb/ers208
- Frossard SM, Khan AA, Warrick EC, Gately JM, Hanson AD, Oldham ML, Sanders DA, Csonka LN (2012) Identification of a third osmoprotectant transport system, the osmU system, in Salmonella enterica. J. Bacteriol. 194: 3861-3871 DOI: 10.1128/JB.00495-12
* With NSF MCB-1153413