Biological rhythms Drosophila

Figure 1. In most examples of biological rhythms, sustained oscillations correspond to the evolution toward a hmit cycle. The limit cycle shown here was obtained in a model for circadian oscillations of the PER protein and per mRNA in Drosophila [107].

Reddy, P., Zehring, W. A., Wheeler, D. A., Pirrotta, V., Hadfield, C., Hall, J. C., and Rosbash, M. (1984). Molecular analysis of the period locus in Drosophila melanogaster and identification of a transcript involved in biological rhythms. Cell 38,701-710. 

An alternative, more detailed model for circadian PER oscillations in Drosophila has been developed independently be Abbot et al. (1995) (M. Rosbasch, personal communication results of that study were first presented at the 4th conference of the Society for Research on Biological Rhythms held in May 1994 in Amelia Island, Florida). That model, which is also based on the negative feedback exerted by PER on per transcription, takes into account a larger number of phosphorylated residues and focuses on the role of PER phosphorylation in delaying the entry of the protein into the nucleus (Curtin et al. 1995). 

Many models for biochemical oscillations rely on positive feedback, as illustrated in this book by the case of glycolytic (chapter 2), cAMP (chapter 5) or (chapter 9) oscillations. Instabilities can, nevertheless, also arise from negative regulation. Together with the models discussed in chapter 10 for the mitotic oscillator in embryonic cells, for which a combination of positive and negative feedback may contribute to periodic behaviour, the model for circadian oscillations in the period protein in Drosophila supports the view that negative feedback is at the core of some of the most important biological rhythms. 

Baylies, M.K., L. Weiner, L.B. Vosshall, L. Saez M.W. Young. 1993. Genetic, molecular, and cellular studies of the per locus and its products in Drosophila melanogaster. In Molecular Genetics of Biological Rhythms, M.W. Yoimg, ed. Marcel Dekker, New York, pp. 123-53. 

Camacho F, Cilio M, Guo Y et al 2001 Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. FEES Lett 489 159-165 Delaunay F, Thisse C, Marchand O, Laudet V, Thisse B 2000 An inherited functional circadian clock in zebrafish embryos. Science 289 297-300 Dunlap J 1998 Circadian rhythms. An end in the beginning. Science 280 1548-1549 Ebisawa T, Uchiyama M, Kajimura N et al 2001 Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome. EMBO Rep 2 342-346 Edery I, Zwiebel LJ, Dembinska ME, Rosbash M 1994 Temporal phosphorylation of the Drosophila period protein. Proc Natl Acad Sci USA 91 2260-2264 Ishida N, Kaneko M, AUada R 1999 Biological clocks. Proc Natl Acad Sci USA 96 8819-8820... 

The study of circadian rhythms has seen a clear acceleration in recent years owing to the combined insights provided by genetics and molecular biology (Feldman, 1982 Hall Rosbash, 1988 Takahashi, 1992, 1993 Dunlap, 1993 Takahashi et al, 1993 Young, 1993). Mutants of circadian rhythms were obtained in Drosophila as early as 1971 (see section 11.2). The use of circadian mutants, recently reviewed by Dunlap (1993), has also proved fruitful in Neurospora (see below) and rodents. Clock mutants have thus been obtained in the hamster (Ralph Menaker, 1988), and the mouse (Vitatema et al, 1994). 

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