Genes controlling biological rhythms have been identified in Drosophila1,2. The best characterized of these genes is called period (per). Although wild-type flies have daily (circadian) rhythms with a periodicity of ~24 h, pers and perl mutants have 19-h and 29-h rhythms, respectively, and per0 mutants are arrhythmic 1. The pers mutation also enhances the sensitivity of the circadian clock to resetting by light stimuli3, and all three types of per mutations affect a much shorter period ultradian rhythm, the 55-s rhythm of the Drosophila courtship song4. A fragment of DNA of ~7 kilobases (kb) encoding a 4.5-kb poly(A)+ RNA restores rhyth-micity when transduced into Drosophila carrying mutations5,6 or chromosomal deletions5 of the per locus. Here we report the sequence of this biologically active segment of DNA. The transcription unit that encodes the 4.5-kb RNA has been mapped, permitting a conceptual translation of a protein of 1,127 amino acids. Several abnormal phenotypes characterized by long-period rhythms are associated with changes in the sequence of untranslated portions of the transcription unit. The structure of some segments of the predicted protein suggests that it is a proteoglycan.
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