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

Abstract

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 <i>cis-</i>QTL in structural genes encoding enzymes and regulatory <i>trans-</i>QTL. Using genome-wide association studies, we mapped QTL for 24 enzyme activities, nine metabolites, three structural components, and biomass in <i>Arabidopsis thaliana</i> We detected strong <i>cis</i>-QTL for five enzyme activities. A <i>cis-</i>QTL for UDP-glucose pyrophosphorylase activity in the <i>UGP1</i> promoter is maintained through balancing selection. Variation in acid invertase activity reflects multiple evolutionary events in the promoter and coding region of <i>VAC-INV</i><i>cis</i>-QTL were also detected for ADP-glucose pyrophosphorylase, fumarase, and phosphoglucose isomerase activity. We detected many <i>trans</i>-QTL, including transcription factors, E3 ligases, protein targeting components, and protein kinases, and validated some by knockout analysis. <i>trans</i>-QTL are more frequent but tend to have smaller individual effects than <i>cis</i>-QTL. We detected many colocalized QTL, including a multitrait QTL on chromosome 4 that affects six enzyme activities, three metabolites, protein, and biomass. These traits are coordinately modified by different <i>ACCELERATED CELL DEATH6</i> alleles, revealing a trade-off between metabolism and defense against biotic stress.