Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock

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Abstract
The period (per) locus, which controls biological rhythms in Drosophila, was originally defined by three chemically induced mutations1. Flies carrying the per° mutation were arrhythmic, whereas pers and perl mutants had circadian behavioural rhythms with 19-hour and 29-hour periodicities, respectively1. Wild-type flies have 24-hour rhythms. Here we compare the per locus DNA sequences of the three mutants with the parental wild-type. The pers and perl mutations lead to amino-acid substitutions, whereas per° introduces an early translation stop (amber). The results indicate that the protein product of per controls biological rhythms. We also report that the abundance of this protein may set the pace of the Drosophila clock. Although circadian rhythms are restored when arrhythmic (per–) Drosophila are transformed with per locus DNA, flies receiving identical transforming DNA segments can produce rhythms with periods that differ by more than 12 hours. Transcription studies reveal a tenfold variation in the level of per RNA among transformed lines. Levels of per RNA are inversely correlated with period length, so that flies with lowest levels of the per product have slow-running biological clocks. On the basis of the combined studies we suggest that perl and pers mutants produce hypoactive and hyperactive per proteins, respectively.