Circadian Timekeeping in Drosophila

Abstract

INTRODUCTORY NOTE 13 This chapter, written in the spring of 1997, describes the first two clock genes to be characterized in Drosophila. A study of the interactions of period and timeless pointed to a simple mechanism that generates self-sustained molecular oscillations, but that can be reset by exposure to cycles of day and night. Four years later, it is remarkable to see how quickly answers to many of the questions posed in this chapter have emerged. Missing pieces of the clock have been found, and insights from the fruit fly have allowed molecular dissection of human cycles of sleep and wakefulness. ORIGINS OF THE GENETIC APPROACH Functional genetic studies of circadian behavioral rhythms were initiated by Konopka and Benzer (1971), who focused on the X chromosome of Drosophila melanogaster. The importance of heredity had been recognized earlier in another Drosophila species, D. pseudoobscura. Genetic differences affected the phase of certain rhythmic behaviors (Pittendrigh, 1967), but no connection to pacemaker organiza-tion was established. Heritable variations in a developmental rhythm with a circadian periodicity also had been observed in Neurospora by Tatum (A. Chovnick, personal communication), but the role of single genes in the control of these rhythms was not established until Feldman and Hoyle's pioneering studies of the Neurospora conidia-tion rhythm (Feldman and Hoyle, 1973).