Oscillating gene

In molecular biology, an oscillating gene is a gene that is expressed in a rhythmic pattern or in periodic cycles. Oscillating genes are usually circadian and can be identified by periodic changes in the state of an organism. Circadian rhythms, controlled by oscillating genes, have a period of approximately 24 hours. For example, plant leaves opening and closing at different times of the day or the sleep-wake schedule of animals can all include circadian rhythms. Other periods are also possible, such as 29.5 days resulting from circalunar rhythms or 12.4 hours resulting from circatidal rhythms. Oscillating genes include both core clock component genes and output genes. A core clock component gene is a gene necessary for to the pacemaker. However, an output oscillating gene, such as the AVP gene, is rhythmic but not necessary to the pacemaker.
History.
The first recorded observations of oscillating genes come from the marches of Alexander the Great in the fourth century B.C. At this time, one of Alexander's generals, Androsthenes, wrote that the tamarind tree would open its leaves during the day and close them at nightfall. Until 1729, the rhythms associated with oscillating genes were assumed to be "passive responses to a cyclic environment". In 1729, Jean-Jacques d'Ortous de Mairan demonstrated that the rhythms of a plant opening and closing its leaves continued even when placed somewhere where sunlight could not reach it. This was one of the first indications that there was an active element to the oscillations. In 1923, Ingeborg Beling published her paper "Über das Zeitgedächtnis der Bienen" ("On the Time Memory of Bees") which extended oscillations to animals, specifically bees In 1971, Ronald Konopka and Seymour Benzer discovered that mutations of the PERIOD gene caused changes in the circadian rhythm of flies under constant conditions. They hypothesized that the mutation of the gene was affecting the basic oscillator mechanism. Paul Hardin, Jeffrey Hall, and Michael Rosbash demonstrated that relationship by discovering that within the PERIOD gene, there was a feedback mechanism that controlled the oscillation. The mid-1990s saw an outpouring of discoveries, with CLOCK, CRY, and others being added to the growing list of oscillating genes.
Molecular circadian mechanisms.
The primary molecular mechanism behind an oscillating gene is best described as a transcription/translation feedback loop. This loop contains both positive regulators, which increase gene expression, and negative regulators, which decrease gene expression. The fundamental elements of these loops are found across different phyla. In the mammalian circadian clock, for example, transcription factors CLOCK and BMAL1 are the positive regulators. CLOCK and BMAL1 bind to the E-box of oscillating genes, such as Per1, Per2, and Per3 and Cry1 and Cry2, and upregulate their transcription. When the PERs and CRYs form a heterocomplex in the cytoplasm and enter the nucleus again, they inhibit their own transcription. This means that over time the mRNA and protein levels of PERs and CRYs, or any other oscillating gene under this mechanism, will oscillate.
There also exists a secondary feedback loop, or 'stabilizing loop', which regulates the cyclic expression of Bmal1. This is caused by two nuclear receptors, REV-ERB and ROR, which suppresses and activates Bmal1 transcription, respectively.
In addition to these feedback loops, post-translational modifications also play a role in changing the characteristics of the circadian clock, such as its period. Without any type of feedback repression, the molecular clock would have a period of just a few hours. Casein kinase members CK1ε and CK1δ were both found to be mammalian protein kinases involved in circadian regulation. Mutations in these kinases are associated with familial advanced sleep phase syndrome (FASPS). In general, phosphorylation is necessary for the degradation of PERs via ubiquitin ligases. In contrast, phosphorylation of BMAL1 via CK2 is important for accumulation of BMAL1.
Examples.
The genes provided in this section are only a small number of the vast amount of oscillating genes found in the world. These genes were selected because they were determined to be the some of most important genes in regulating the circadian rhythm of their respective classification.