Unique Hmgn2 Orthologous Variant Modulates Shape Preference Behavior in Medaka Fish

Diversification of protein sequences contributes to the variation of physiological traits. In this study, using medaka fish (Oryzias latipes) as a model, we identified a novel protein variant influencing shape preference behavior. Re-analysis of sequencing data revealed that LOC101156433, previously annotated as a non-protein- coding gene, encodes a divergent Hmgn2 variant undetectable by standard homology searches. This unique Hmgn2 in medaka shows non-standard subnuclear localization, and mutants exhibited a reduction in certain regions of the telencephalon and a loss of shape preference. These results not only establish a direct association between amino acid sequence variation and the development of new molecular properties and behavioral adaptations but also highlight new clues toward understanding the visual shape perception system in fish.