Shigeyoshi, Y., Meyer-Bernstein, E., Yagita, K., Fu, W., Chen, Y., Takumi, T., Schotland, P., Sehgal, A., Okamura, H. (2002). Restoration of circadian behavioural rhythms in a period null Drosophila mutant (per01) by mammalian period homologues mPer1 and mPer2.  Genes Cells 7(2): 163--171.

FBrf0147044

Research paper

Recent molecular studies suggest that mammals and Drosophila utilize similar components to generate circadian (approximately equal to 24 h) rhythms. The first identified circadian clock gene, the period (per) gene, is indispensable for behavioural rhythms in Drosophila and is represented in mammals by three orthologues, the relative roles of which are not known. In this study, we investigated the functional conservation of per by introducing the mouse mPer1 and mPer2 genes, driven by the Drosophila timeless (tim) promoter, into Drosophila melanogaster.Behavioural assays showed that both mPer constructs restored rhythms in per(01) flies that are otherwise arrhythmic due to a lack of endogenous per protein (PER). However, the rhythms restored by mPer2 were generally stronger and differed in periodicity from those restored by mPer1. In rhythmic transgenic flies, mPER proteins were expressed in lateral neurones and/or many cells in optic lobe. In addition, cell culture experiments indicated that the Drosophila PER partner, TIM, can form a complex with each of these two mammalian proteins.This study demonstrates that both mPer1 and mPer2 can function as clock components, and has implications for a functional analysis of the different per genes.