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 calle d Jrk, manifests dominant effects: heterozygous flies have a period al teration and half are arrhythmic, while homozygous flies are uniformly arrhythmic. Furthermore, these flies express low levels of the two cl ock proteins, PERIOD (PER) and TIMELESS (TIM), due to low per and tim transcription. Mapping and cloning of the Jrk gene indicates that it e ncodes the Drosophila homolog of mouse Clock. The mutant phenotype res ults from a premature stop codon that eliminates much of the putative activation domain of this bHLH-PAS transcription factor, thus explaini ng the dominant features of Jrk. The remarkable sequence conservation strongly supports common clock components present in the common ancest or of Drosophila and mammals.