A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless

We report the identification, characterization, and cloning of a novel Drosophila circadian rhythm gene, dClock. The mutant, initially called Jrk, manifests dominant effects: heterozygous flies have a period alteration and half are arrhythmic, while homozygous flies are uniformly arrhythmic. Furthermore, these flies express low levels of the two clock proteins, PERIOD (PER) and TIMELESS (TIM), due to low per and tim transcription. Mapping and cloning of the Jrk gene indicates that it encodes the Drosophila homolog of mouse Clock. The mutant phenotype results from a premature stop codon that eliminates much of the putative activation domain of this bHLH-PAS transcription factor, thus explaining the dominant features of Jrk. The remarkable sequence conservation strongly supports common clock components present in the common ancestor of Drosophila and mammals.