Restoration of circadian behavioural rhythms by gene transfer in Drosophila

Abstract

The per locus of Drosophila melanogaster has a fundamental role in the construction or maintenance of a biological clock. Three classes of per mutations have been identified: per^l mutants have circadian behavioural rhythms with a 29-h rather than a 24-h period, per^s mutants have short-period rhythms of 19 h, and per⁰ mutants have no detectable circadian rhythms^1–4. Each of these mutations has a corresponding influence on the 55-s periodicity of male courtship song⁵. Long-and short-period circadian rhythm phenotypes can also be obtained by altering the dosage of the wild-type gene⁴: for example, females carrying only one dose of this X-linked gene have circadian rhythms with periodicities about 1 h longer than those carrying two doses. In a previous report⁶, cloned DNA was used to localize several chromosomal rearrangement breakpoints that alter per locus function. The rearrangements all affected a 7-kilobase (kb) interval that encodes a 4.5-kb poly(A)⁺ RNA. We report here that when a 7.1-kb fragment from a per⁺ fly, including the sequences encoding the 4.5-kb transcript, is introduced into the genome of a per⁰ (arrhythmic) fly by P element-mediated transformation, circadian rhythmicity of behaviour such as eclosion and locomotor activity is restored. The transforming DNA complements per locus deletions and is transcribed, forming a single 4.5-kb poly(A)⁺ RNA comparableto that produced by wild-type flies.