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A clock gene contributes to a biological timing mechanism, for example the approximately daily circadian rhythm. Its product can participate in a feedback loop whose delayed activity changes the later production or action of other clock components. The term can describe a functional class; it should not be confused with the particular gene named CLOCK.

In the foundational fly experiment, three mutations assigned to the same locus produced arrhythmic behaviour or approximately 19-hour and 28-hour rhythms. The investigators measured both emergence timing in populations and locomotor activity in individuals. This linked inherited variation to an internal timing mechanism, rather than simply to an immediate response to light. ^[ref]

Ronald J. Konopka coauthored the 1971 identification of circadian rhythm mutants in Drosophila melanogaster with Seymour Benzer. Their screen produced arrhythmic, short-period and long-period flies. The combination showed that a mutation can alter the period of an internal timing mechanism, rather than only disabling movement altogether.^[ref]

Automatic collection measured when adults emerged, and infrared detectors measured individual locomotion. Tests in constant darkness separated free-running timing from direct light-driven activity. Mapping and complementation indicated that the three mutations affected the same functional gene on the X chromosome, providing an entry point for the genetics of biological clocks.^[ref]

Seymour Benzer helped turn the study of behavior into an experimental problem in genetics. With Ronald J. Konopka, he reported fruit-fly mutations that abolished daily rhythmicity or changed its period to approximately 19 or 28 hours. Both adult emergence and individual locomotor activity were affected.^[ref]

Flies were tested in constant darkness, while infrared monitoring recorded individual movement without imposing a daily light cycle. Persistence of altered timing under those conditions supported an internal circadian rhythm mechanism, rather than merely a different immediate response to the lamps switching on. The mutations mapped to the same functional gene on the X chromosome.^[ref]