Genome-Wide Association Mapping Reveals That Specific and Pleiotropic Regulatory Mechanisms Fine-Tune Central Metabolism and Growth in Arabidopsis

Central metabolism is a coordinated network that is regulated at multiple levels by resource availability and by environmental and developmental cues. Its genetic architecture has been investigated by mapping metabolite quantitative trait loci (QTL). A more direct approach is to identify enzyme activity QTL, which distinguishes between cis-QTL in structural genes encoding enzymes and regulatory trans-QTL. Using genome-wide association studies, we mapped QTL for 24 enzyme activities, 9 metabolites, 3 structural components, and biomass in Arabidopsis thaliana. We detected strong cis-QTL for five enzyme activities. A cis-QTL for UDP-glucose pyrophosphorylase activity (UGP) in the UGP1 promoter is maintained through balancing selection. Variation in acid invertase activity (aINV) reflects multiple evolutionary events in the promoter and coding region of VAC-INV. Cis-QTL were also detected for ADP-glucose pyrophosphorylase (AGP), fumarase (FUM), and phosphosglucose isomerase activity (PGI). We detected many trans-QTL, including transcription factors, E3 ligases, protein targeting components, and protein kinases and validated some by knockout analysis. Trans-QTL are more frequent but tend to have smaller individual effects than cis-QTL. We detected many co-localized QTL, including a multi-trait QTL on chromosome 4 that affects six enzyme activities, three metabolites, protein, and biomass. These traits are coordinately modified by different ACCELERATED CELL DEATH6 alleles, revealing a trade-off between metabolism and defense against biotic stress.