Karageorgi, M., Lyulina, A.S., Bitter, M.C., Lappo, E., Greenblum, S.I., Mouza, Z.K., Tran, C.T., Huynh, A.V., Oken, H., Schmidt, P., Petrov, D.A. (2025). Beneficial reversal of dominance maintains a large-effect resistance polymorphism under fluctuating insecticide selection.  Nat. Ecol. Evol. 9(11): 2145--2160.

FBrf0263868

Research paper

Large-effect standing genetic variation is commonly found in natural populations and must be maintained in the face of directional natural selection. Theory suggests that under fluctuating selective pressures, beneficial reversal of dominance-where alleles are dominant when beneficial and recessive when deleterious-can strongly stabilize large-effect polymorphisms. However, empirical evidence for this mechanism remains limited because testing requires measurements of selection and dominance in fitness in natural conditions. Here we investigate large-effect fitness polymorphisms at the Ace locus of Drosophila melanogaster that confer insecticide resistance and persist at intermediate frequencies worldwide. By combining laboratory and large-scale field mesocosm experiments with insecticide manipulation and mathematical modelling, we show that the benefits of the resistant Ace alleles are dominant in pesticide-rich environments, while their fitness costs are recessive in pesticide-free environments. We further show that temporally fluctuating insecticide selection generates chromosome-scale genomic perturbations at sites linked to the resistant Ace alleles. Overall, our results suggest that beneficial reversal of dominance under temporally fluctuating selection might plausibly contribute to the maintenance of functional genetic variation and, by stabilizing large frequency fluctuations, impact long-range patterns of genomic variation.

PMC13227945 (PMC) (EuropePMC)