Timeless and diapause in Drosophila

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Hibernation is a protective state of suspended animation that comes around every season in plants and animals that live in the temperate zones of the world. In insects, this seasonal cycle is called diapause, and is stimulated by the reduction in daylength as winter approaches. The other great rhythm on this planet is the circadian cycle which is the daily 24 hour cycle that we all recognise as our 'body clock'. Recently we have found a connection between a gene called timeless that controls the 24 hour rhythm of the geneticists favourite pet, the fruitfly, and the seasonal diapause cycle. A new mutation in the timeless gene, ls-tim, occurred in south-eastern Italy about 8000 years ago, a few thousand years after the last glaciation when flies invaded Europe from Africa This mutation allows the fly to make two types of TIM protein, L-TIM and S-TIM, whereas the ancient gene, s-tim can only make S-TIM. The new mutation, ls-tim, is spreading under natural selection, because it adapts the fly to the seasonal environment of Europe. It does this by reducing the light sensitivity of the ls-tim fly's diapause mechanism. Thus, even in relatively long days, ls-tim flies 'see' shorter days, and this stimulates them diapause earlier than in s-tim flies. The earlier the fly goes into diapause in Europe, the better its chances of surviving the oncoming winter. In addition, the 24 hour circadian clock of ls-tim is also less light-sensitive and this too is adaptive in Europe, which has very exotic photoperiods in summer which causes the fly's biorhythms to creak. Consequently, L-TIM attenuates the fly's photosensitivity for both circadian and seasonal behaviours, and that is perhaps why this new mutation has spread in Europe. Biochemically, the L-TIM protein is less light sensitive because of its weak physical interaction with a circadian photoreceptor called Cryptochrome. The ls-tim mutation creates a site in the L-TIM protein that is not shared in S-TIM. This new site may be phosphorylated, a protein modification that may alter the shape and stability of L-TIM. This may provide the biochemical clue for why ls-tim flies behave differently. We shall study this site to see whether it is indeed phosphorylated. We shall also investigate whether ls-tim flies change the ratios of the L-TIM and S-TIM they produce under the short days and cold temperature that produce diapause. In addition we will study under these conditions how strongly L-TIM and S-TIM 'touch' the photoreceptor Cryptochrome in the fly's brain and eyes, as this physical interaction provides the light input into the circadian mechanism. There has been a long running debate about whether the circadian clock contributes to diapause. Using the timeless gene, we shall genetically dissect the fly's nervous system in order to investigate which groups of neurons are important for diapause. Because the 24 hour clock neurons are well known and easily identified, we should be able to see whether these cells are relevant for the fly's hibernation. We can then visualise L-TIM and S-TIM protein in the relevant cells of ls-tim flies under diapause conditions, to see whether the two proteins behave differently. Insect diapause is a potential target for the control of medical and agricultural pests in temperate regions, and so our work may have practical spin-offs in future.