Product of per locus of Drosophila shares homology with proteoglycans

Abstract

Genes controlling biological rhythms have been identified in Drosophila^1,2. The best characterized of these genes is called period (per). Although wild-type flies have daily (circadian) rhythms with a periodicity of ∼24 h, per^s and per^l mutants have 19-h and 29-h rhythms, respectively, and per⁰ mutants are arrhythmic¹. The per^s 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 mutations^5,6 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.