Metabolome-scale genome-wide association studies reveal chemical diversity and genetic control of maize specialized metabolites

Authors: ZHOU, SHAOQUN - Boyce Thompson Institute; KREMLING, KARL - Cornell University; BANDILLO, NONOY - Cornell University; RICHTER, ANNETT - Boyce Thompson Institute; ZHANG, YING - Boyce Thompson Institute; AHERN, KEVIN - Boyce Thompson Institute; ARTYUKHIN, ALEXANDER - Boyce Thompson Institute; HUI, JOSHUA - Boyce Thompson Institute; YOUNKIN, GORDON - Boyce Thompson Institute; SCHROEDER, FRANK - Boyce Thompson Institute; Buckler, Edward - Ed; JANDER, GEORG - Boyce Thompson Institute

Submitted to: The Plant Cell
Publication Type: Review Article
Publication Acceptance Date: 3/27/2019
Publication Date: 5/28/2019
Citation: Shaoqun, Z., Kremling, K.A., Bandillo, N., Richter, A., Zhang, Y.K., Ahern, K.R., Artyukhin, A.B., Hui, J.X., Younkin, G.C., Schroeder, F.C., Buckler IV, E.S., Jander, G. 2019. Metabolome-scale genome-wide association studies reveal chemical diversity and genetic control of maize specialized metabolites. The Plant Cell. 31:937-955. https://doi.org/10.1105/tpc.18.00772.
DOI: https://doi.org/10.1105/tpc.18.00772

Interpretive Summary: Plants defend themselves against pests and diseases by producing specialized metabolites. Understanding how these metabolites are synthesized, regulated and distributed will facilitate the development of stress-resistant crops that can grow in stressful environments. Identifying natural variations in different genotypes for specific metabolites can be used for breeding crops adapted to stressful environments. This study produced a metabolome-scale association resource that includes thousands of known and uncharacterized maize metabolites. This resource led to the discovery of a gene related to class of maize metabolites that has not yet been investigated. This resource also identified hotspots in the maize genome that had a disproportional impact on numerous metabolites, demonstrating that metabolites associated with shared genetic elements tend to be similar in chemical structure. Finally, this study demonstrated that both tissue type and maize population have significant impact on the abundance of specialized metabolites. With this high-resolution metabolite mapping resource, further studies can be conducted to demonstrate the relationship between metabolites and associated genes or agronomic traits, and thus this is a valuable resource for bridging the gap between genotype and phenotype.

Technical Abstract: Cultivated maize (Zea mays) has retained much of the genetic diversity of its wild ancestors. Here, we performed nontargeted liquid chromatography-mass spectrometry metabolomics to analyze the metabolomes of the 282 maize inbred lines in the Goodman Diversity Panel. This analysis identified a bimodal distribution of foliar metabolites. Although 15% of the detected mass features were present in >90% of the inbred lines, the majority were found in <50% of the samples. Whereas leaf bases and tips were differentiated by flavonoid abundance, maize varieties (stiff-stalk, nonstiff-stalk, tropical, sweet maize, and popcorn) showed differential accumulation of benzoxazinoid metabolites. Genome-wide association studies (GWAS), performed for 3,991 mass features from the leaf tips and leaf bases, showed that 90% have multiple significantly associated loci scattered across the genome. Several quantitative trait locus hotspots in the maize genome regulate the abundance of multiple, often structurally related mass features. The utility of maize metabolite GWAS was demonstrated by confirming known benzoxazinoid biosynthesis genes, as well as by mapping isomeric variation in the accumulation of phenylpropanoid hydroxycitric acid esters to a single linkage block in a citrate synthase-like gene. Similar to gene expression databases, this metabolomic GWAS data set constitutes an important public resource for linking maize metabolites with biosynthetic and regulatory genes.