Natural noncoding <i>pumilio</i> variants retune value-coding interneurons to bias <i>Drosophila</i> oviposition decisions.

Abstract

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 <i>Drosophila</i>: where to oviposit. Although laboratory flies (<i>w¹¹¹⁸</i>) reject sucrose for a plain option, a wild-caught African strain accepts sucrose. This decision difference maps to three African-specific intronic SNPs in <i>pumilio</i> (<i>pum</i>), an RNA binding translational repressor. These SNPs down-regulate <i>pum</i>, derepressing its target, the sodium channel <i>paralytic</i> (<i>para</i>), in a pair of GABAergic interneurons that encode option value. Elevated <i>para</i> boosts neuronal excitability, compresses value contrast between sucrose and plain options, and promotes sucrose acceptance. Selectively reducing <i>pum</i> or overexpressing <i>para</i> 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.