Natural noncoding pumilio variants retune value-coding interneurons to bias Drosophila oviposition decisions
- Dorsa Motevalli
- Robert Alfredson
- Sydney Fogleman
- Emmanuel Medrano
- Yang Chen
- William I. Silander
- Toshihide Hige
- Ulrich Stern
- Chung-Hui Yang
2026-05-12
How natural regulatory genetic variation creates innate biases in economic decisions through modifying circuit structure and function is rarely explored. Here, we trace this link in a simple value-based decision in Drosophila : where to oviposit. Although laboratory flies ( w 1118 ) reject sucrose for a plain option, a wild-caught African strain accepts sucrose. This decision difference maps to three African-specific intronic SNPs in pumilio ( pum ), an RNA binding translational repressor. These SNPs down-regulate pum , derepressing its target, the sodium channel paralytic ( para ), in a pair of GABAergic interneurons that encode option value. Elevated para boosts neuronal excitability, compresses value contrast between sucrose and plain options, and promotes sucrose acceptance. Selectively reducing pum or overexpressing para in these neurons converts the laboratory flies’ physiology and behavior to the African phenotype. These findings offer a genome-to-circuit-to-behavior framework, revealing how subtle regulatory polymorphisms fine-tune circuit properties to diversify environment-appropriate decision biases in nature.