Trans-regulatory loci shape natural variation of gene expression plasticity in Arabidopsis

Organisms regulate gene expression in response to environmental cues, a process known as plasticity, to adjust to changing environments. Research into natural variation and the evolution of plasticity frequently studies cis -regulatory elements with theory suggesting they are more important evolutionarily than trans -regulatory elements. Genome-wide association studies have supported this idea, observing a predominance of cis -loci affecting plasticity. However, studies in structured populations provide a contrasting image, raising questions about the genetic architecture of natural variation in plasticity. To circumvent potential statistical difficulties present in genome-wide association studies, we mapped loci underlying transcriptomic plasticity in response to salicylic acid using recombinant inbred lines generated from two random Arabidopsis thaliana accessions. We detected extensive transgressive segregation in the salicylic acid response, suggesting that plasticity to salicylate in Arabidopsis is polygenic. Most loci (>75%) underlying this variation act in trans , especially for loci influencing plasticity. Trans -acting loci were enriched in genome hotspots, with predominantly small effect sizes distributed across many genes. This could potentially explain their under-discovery in genome-wide association studies. This work reveals a potentially important role for trans -acting loci in plastic expression responses, with implications for understanding plant adaptation to different environments.