Diapause is the classic adaptation to seasonality in arthropods, and its expression can result in extreme lifespan extension as well as enhanced resistance to environmental challenges. Little is known about the underlying evolutionary genetic architecture of diapause in any organism. Drosophila melanogaster exhibits a reproductive diapause that is variable within and among populations; the incidence of diapause increases with more temperate climates and has significant pleiotropic effects on a number of life history traits. Using quantitative trait mapping, we identified the RNAbinding protein encoding gene couch potato (cpo) as a major genetic locus determining diapause phenotype in D. melanogaster and independently confirmed this ability to impact diapause expression through genetic complementation mapping. By sequencing this gene in samples from natural populations we demonstrated through linkage association that variation for the diapause phenotype is caused by a single Lys/Ile substitution in one of the six cpo transcripts. Complementation analyses confirmed that the identified amino acid variants are functionally distinct with respect to diapause expression, and the polymorphism also shows geographic variation that closely mirrors the known latitudinal cline in diapause incidence. Our results suggest that a naturally occurring amino acid polymorphism results in the variable expression of a diapause syndrome that is associated with the seasonal persistence of this model organism in temperate habitats.cline ͉ diapause ͉ life history ͉ mapping ͉ tradeoff N atural populations encounter environmental stresses that diminish individual fitness, and these stresses are variable across space and time. It is predicted that the resulting natural selection often leads to a situation in which no genotype has the highest fitness across all environments, and polymorphism is maintained. This concept is pervasive in arguments about the evolution of life history variation and associated genetic tradeoffs (1). However, the expected molecular polymorphism associated with life history tradeoffs and adaptation remains elusive. Although we would expect these phenomena to be universal, the complexities of genetic dissection of such variation suggest that the best opportunity to identify the genetic basis for life history variation lies in the study of the genetic models in their natural populations (2).Drosophila melanogaster is a human commensal that has spread from areas of Sub-Saharan Africa to Europe and Asia, possibly over the last 5,000 to 16,000 years, and into the Western Hemisphere and Australia in the past several hundred years (3-5). This worldwide expansion from the tropics has required adaptation to the pronounced seasonality present in temperate habitats, and there are many examples of both single-gene polymorphism and quantitative trait variation that show geographic patterns associated with the transition from tropical to temperate climates in this species (6, 7). There also is good evidence that D. melanogaster ov...