A biological clock in Drosophila.

The per locus plays a central role in the organization and function of the Drosophila biological clock. The gene has been mapped to a 7-kb DNA segment by physically locating the breakpoints of several chromosomal rearrangements that disrupt per function. This DNA contains a single transcription unit which produces a 4.5-kb poly(A)+ RNA. No oscillation in the synthesis of this transcript is detected when per expression is followed over a 24-hour cycle of light and dark. When wild-type DNA containing only this transcription unit is transferred to the genome of a per0 (arrhythmic) fly by P-element-mediated transformation, the 4.5-kb RNA is produced and rhythmic behavior is restored with high penetrance of the rhythmic phenotype. This transforming DNA will also complement chromosomal deletions that include the per locus and adjoining transcription units, indicating that only one gene in this chromosomal interval plays a measureable role in the production of circadian rhythms. Transformed flies having rhythms with longer than wild-type periodicity underproduce the 4.5-kb RNA. We suggest that the periodicity of circadian rhythms in Drosophila is determined by the level of expression of a per locus protein encoded by the 4.5-kb transcript. We have found DNA homologous to the per locus in several species of vertebrates. DNA exhibiting very high homology to a portion of the per locus has been cloned from the mouse and the DNA sequence of the conserved segment has been determined. Mouse and fly DNAs both appear to code for long protein segments composed exclusively of alternating threonine and glycine or serine and glycine residues.