Functional polymorphism of CYCLE underlies the diapause variation in moths

Diapause is a common seasonal adaptive strategy that regulates annual timing in insects. Very few causal loci underlying diapause variation have yet been identified. By leveraging cross-mapping and genome-wide association analysis, we identified the N terminus of the clock protein CYCLE as a major causal effector underlying embryonic diapause differences in the silk moth. We found that the nondiapause phenotype in polyvoltine strains results from a specific deletion that disrupts an alternative isoform of CYCLE. We further demonstrated that different CYCLE isoforms contribute to a functional diversity in modulating circadian rhythms and diapause, which has been preserved in Lepidoptera for at least 110 million years. Our study proposes a model that explains how adaptive phenotypes can evolve rapidly without affecting related essential functions.