title: Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.
abstract: BACKGROUND
  Central carbon metabolism (CCM) is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays), the most diverse model crop species, to study the genetics of CCM is a particularly attractive system.
  
  
  RESULTS
  We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41), in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis), the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication.
  
  
  CONCLUSIONS
  Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.
authors.affiliation: Institute for Genomic Diversity, Cornell University, Ithaca, New York, United States of America. nz45@cornell.edu
authors.forename: Nengyi
authors.initials: N
authors.lastname: Zhang
authors.forename: Amit
authors.initials: A
authors.lastname: Gur
authors.forename: Yves
authors.initials: Y
authors.lastname: Gibon
authors.forename: Ronan
authors.initials: R
authors.lastname: Sulpice
authors.forename: Sherry
authors.initials: S
authors.lastname: Flint-Garcia
authors.forename: Michael D
authors.initials: MD
authors.lastname: McMullen
authors.forename: Mark
authors.initials: M
authors.lastname: Stitt
authors.forename: Edward S
authors.initials: ES
authors.lastname: Buckler
mesh_terms: D019943:Amino Acid Substitution; D002244:Carbon / Q000378:metabolism*; D018556:Crops, Agricultural; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D003313:Zea mays / Q000235:genetics*
chemical_list: D002244:Carbon; D007521:Isocitrate Dehydrogenase