Transcription translation feedback loop

Transcription-translation feedback loop (TTFL) is a cellular model for explaining circadian rhythms in behavior and physiology. Widely conserved across species, the TTFL is auto-regulatory, in which transcription of clock genes is regulated by their own protein products.

Discovery

Circadian rhythms have been documented for centuries. For example, French astronomer Jean-Jacques d'Ortous de Mairan noted the periodic 24-hour movement of Mimosa plant leaves as early as 1729. However, science has only recently begun to uncover the cellular mechanisms responsible for driving observed circadian rhythms. The cellular basis of circadian rhythms is supported by the fact that rhythms have been observed in single-celled organisms.

Beginning in the 1970s, experiments conducted by Ron Konopka and colleagues, in which forward genetic methods were used to induce mutation, revealed that Drosophila melanogaster specimens with altered period (Per) genes also demonstrated altered periodicity. As genetic and molecular biology experimental tools improved, researchers further identified genes involved in sustaining normal rhythmic behavior, giving rise to the concept that internal rhythms are modified by a small subset of core clock genes. Hardin and colleagues (1990) were the first to propose that the mechanism driving these rhythms was a negative feedback loop. Subsequent major discoveries confirmed this model; notably experiments led by Thomas K. Darlington and Nicholas Gekakis in the late 1990s that identified clock proteins and characterized their methods in Drosophila and mice, respectively.