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Background  The mosquito  Wyeomyia smithii  overwinters in a larval diapause that is initiated, maintained and terminated by day length (photoperiod). We use a forward genetic approach to investigate transcriptional events involved in the termination of diapause following exposure to long-days.    Methods/Principal Findings  We incorporate a novel approach that compares two populations that differentially respond to a single day length. We identify 30 transcripts associated with differential response to day length. Most genes with a previously annotated function are consistent with their playing a role in the termination of diapause, in downstream developmental events, or in the transition from potentially oxygen-poor to oxygen-rich environments. One gene emerges from three separate forward genetic screens as a leading candidate for a gene contributing to the photoperiodic timing mechanism itself (photoperiodic switch). We name this gene  photoperiodic response gene 1  ( ppdrg1 ).  WsPpdrg1  is up-regulated under long-day response conditions, is located under a QTL for critical photoperiod and is associated with critical photoperiod after 25 generations of recombination from a cross between extreme phenotypes.    Conclusions  Three independent forward genetic approaches identify  WsPpdrg1  as a gene either involved in the photoperiodic switch mechanism or very tightly linked to a gene that is. We conclude that continued forward genetic approaches will be central to understanding not only the molecular basis of photoperiodism and diapause, but also the evolutionary potential of temperate and polar animal populations when confronted with rapid climate change.

Microarrays Reveal Early Transcriptional Events during the Termination of Larval Diapause in Natural Populations of the Mosquito, Wyeomyia smithii