Genetic screens for clock mutants in Drosophila.

The isolation and analysis of mutant flies (Drosophila melanogaster) with altered circadian rhythms have led to an understanding of circadian rhythms at the molecular level. This molecular mechanism elucidated in fruit flies is similar to the mechanism of the human circadian clock, which confers 24-h rhythmicity to our sleep/wake behavior, as well as to many other aspects of our cellular and organismal physiology. In fruit flies, genes can be mutated to abolish circadian rhythms (i.e., produce arrhythmia) or alter the period of the circadian rhythm; these genes encode key components of the circadian oscillator mechanism. Other mutations have identified components of the input pathways (by which light and temperature synchronize the circadian clock to environmental cycles) or output pathways (which connect the circadian oscillator to the physiological response). Mutations in genes are typically generated by chemical mutagenesis or mutagenesis with transposable elements. Flies with mutagenized chromosomes are processed in a series of genetic crosses, which allow specific chromosomes to be screened for semidominant mutations, recessive mutations, enhancer/suppressor mutations, or genes that can be overexpressed to alter circadian rhythms. Circadian phenotypes, which are assayed to identify mutants, include eclosion (emergence of the adult from the pupal case), locomotor activity (similar to human sleep?wake behavior), and circadian oscillations of gene expression. It is argued that screens for new circadian genes will continue to reveal novel components of the circadian mechanism.