We don't see it, we don't hear it, yet our internal clock ticks and controls our everyday life more than we realise. Only when we live against our internal clock do we become aware of its arcane rhythm, for instance when we suffer jet lag after a long-distance flight. What makes the internal clock so important is that it orchestrates vital physiological functions, such as body temperature or blood pressure.
Internal clocks are synchronized by external rhythms. Nature is affected by two of them, the daily sun cycle and the annual cycle of the seasons. Correspondingly, two types of internal clocks exist in animals and plants: a circadian and a photoperiodic clock; regulating daily and seasonal activities,respectively. The circadian clock is synchronized by light–dark cycles,the photoperiodic clock by day length. It is an old debate whether the fundamental mechanisms underlying the circadian clock also account for the photoperiodic clock. In two studies published recently, a British and Italian team of scientists led by Charalambos Kyriacou and Rodolfo Costa showed that both clocks are based on distinct genetic programs, suggesting that the mechanisms underlying both clocks are different.
Remarkable progress has been made in elucidating the mechanism of the circadian clock, particularly in Drosophila melanogaster. A big breakthrough was the discovery of circadian clock genes, such as timeless (tim), whose gene products oscillate in a daily rhythm, or cryptochrome (cry), which encodes a photoreceptor, CRY, required for the entrainment of circadian rhythms to light–dark cycles by influencing, among others, oscillations in TIM protein levels. By contrast, the molecular basis of the photoperiodic clock is largely unknown. To shed light on it, the team investigated the photoperiodic timing of diapause, the suspension of insects' development as an adaptation to changing seasons. They did this for the first time in the `clock model'Drosophila and found that diapause in European populations occurs more frequently at shorter day lengths and at northern latitudes.
When the scientists analyzed the tim gene in different Drosophila populations, they found two natural alleles, s-tim, which encodes the shorter, ancestral variant of the TIM protein (S-TIM), and ls-tim, which encodes a longer, newly derived variant (L-TIM) of the TIM protein. It was previously known that CRY synchronizes the circadian clock by binding to TIM in a light-dependent manner and thereby promoting its degradation. But does the newly discovered L-TIM exhibit the same binding properties as S-TIM? Performing interaction assays in yeast, the team showed that L-TIM binds less tightly to the CRY photoreceptor. As a consequence of altered binding properties, photosensitivity of the circadian clock declines due to increased L-TIM stability. Thus, fly populations with different TIM alleles set their internal clock with different accuracies.
However, does the discovered allelic variation also affect the photoperiodic timer? To answer this question, the team carefully analyzed the allele frequencies in natural populations. They found that the alleles have spread unevenly throughout Europe. The ancestral s-tim is more prevalent in the north, with the younger ls-tim more in southern Europe. Analysis of homozygous flies showed that ls-tim flies generally undergo diapause more frequently than s-tim flies,suggesting that ls-tim confers an advantage by making the flies more adaptable to the changing European seasons. However, the team found no hint of an interaction between the tim genotype and the photoperiod in the induction of diapause, implying that the circadian and the photoperiodic clock use different mechanisms.
The clock gene timeless hence appears to have two functions in Drosophila. In addition to its key role as an oscillator of the circadian clock, it directly affects initiation of diapause without biasing the photoperiodic clock. Although the team of Kyriacou and Costa provide important clues on timeless function, the molecular mechanisms underlying the photoperiodic clock are still elusive.