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

Cultivated maize (Zea mays) retains much of the genetic diversity of its wild ancestors. Non-targeted HPLC-MS metabolomics using the Good Diversity Panel of maize inbred lines identified a bimodal distribution of foliar metabolites. Although 15% of the detected mass features were present in g90% of the inbred lines, the majority were found in l50% of the samples. Whereas leaf bases and tips were differentiated by flavonoid abundance, maize varieties (stiff-stalk, non-stiff-stalk, tropical, sweet corn, 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 metabolically 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 dataset constitutes an important public resource for linking maize metabolites with biosynthetic and regulatory genes.