Drosophila fruit flies are commonly used for research on biological, or circadian, clocks because of the relative ease of finding mutants with non-24-hour rhythms and then identifying the genes underlying the altered behavior. These studies in fruit flies have allowed the identification of similar "clock genes" in mammals, which function in a similar manner in mammals as they do in a fly's clock. However, prior to this study, biologists had concluded that the role of one protein--Cryptochrome (Cry)--was quite different between flies and mammals. In fruit flies, Cry is a circadian photoreceptor, which helps light reset the biological clock with changing seasons, or in jet lag-style experiments (in which light is manipulated to mimic the experience of traveling over multiple time zones) in the lab. In mammals, however, Cry assists in the 24-hour rhythmic expression of clock genes and has nothing to do with re-setting the clock.
The researchers sought to determine additional roles for Cry in fruit flies by testing the rhythmic expression of clock genes in flies with either a mutant version of Cry, or with Cry produced at artificially high levels. In both cases, they found that the clock had stopped – with high levels of clock gene expression when Cry was mutated, and low levels when Cry was over-produced. These results indicated that Cry normally inhibits clock gene expression in many clock cells – just as it does in the mammalian clock.
"In addition to finding a new function for Cryptochrome, the results reinforce that notion that fruit flies provide an excellent model for understanding the human biological clock that drives sleep/wake cycles and many other processes that contribute to our overall health," said Blau.
The research was supported by a grant from the National Institutes of Health.
Journal
Current Biology