Molecular control of Drosophila circadian rhythms

Abstract

The ubiquity of circadian rhythms testifies to their adaptive significance. Studies in Drosophila melanogaster have greatly advanced the understanding of circadian rhythms at molecular level. To date, at least seven genes in Drosophila have been described and shown to participate in transcription–translation based feedback loops that comprise the central oscillator controlling overt circadian behaviors. Many of these genes have functional homologues in mammals. There has also been recent progress in describing, at the molecular level, how temporal information from the environment is conveyed to the central oscillator, and how, in turn, that information is conveyed to the rest of the organism. Along with he recent explosion in the understanding of the molecular underpinnings of the clock, it has also been observed that the work described in this chapter is applicable to other systems. Period (per), timeless (tim), dClock (dClk), cycle (cyc), doubltime (dbt), and cryptochrome (cry) all have homologues in the mammalian system, many of them functional counterparts. There are 3 mammalian per homologues that cycle with a circadian rhythm and function as negative elements in a feedback loop. Mammalian Clock and cyc can heterodimerize and activate transcription from E-boxes, and tau (mammalian dbt) has been shown to phosphorylate the mper proteins in vitro. There are some important differences between the mammalian and Drosophila systems. The two known mammalian cry homologues do not mediate circadian photoreception, but instead, appear to have a role as negative elements in the feedback loop, and are required for behavioral rhythmicity. tim's role in the mammalian system is still unknown; although, in contrast with Drosophila, tim is essential for embryonic development. Light sensitivity does not appear to be mediated by a light sensitive protein, but rather via photic induction of the mper RNAs. In addition to the molecular conservation seen in animals, the mechanism of the transcription–translation based negative feedback loop is found across the phyla in cyanobacteria, fungi, and plants.