Cis-Combination of the Classic perS and perL Mutations Results in Arrhythmic Drosophila with Ectopic Accumulation of Hyperphosphorylated PERIOD Protein:

The 1st circadian “clock” gene identified was the X-linked period (per) gene in Drosophila melanogaster. In the pioneering initial report, Konopka and Benzer (1971) characterized 3 alleles of per that shortened (perS; ~19 h), lengthened (perL; ~29 h), or abolished (per0) circadian behavioral rhythms. They also showed that transheterozygotes carrying the perS and perL mutations exhibit robust behavioral rhythms with nearly normal periods of ~23 h, highlighting the semidominant nature of many clock mutants. In this study, per0 flies bearing a doubly mutated per transgene that carries both the perS and perL alleles (per0; perS/L) were analyzed for behavioral and molecular rhythms. Unlike singly mutated versions, the per0;per S/L transgenic flies are arrhythmic in constant dark conditions and exhibit little, if any, entrainment to daily light—dark cycles. In a wildtype per+ background, expression of per S/L abolishes behavioral rhythms, indicating that it functions in a transdominant negative fashion. Biochem...