circadian rhythm circadian rhythm a circadian rhythm (/sərˈkeɪdiən/), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. it can refer to any process that originates within an organism (i.e., endogenous) and responds to the environment (entrained by the environment). these 24-hour rhythms are driven by a circadian clock, and they have been widely observed in animals, plants, fungi and cyanobacteria. circadian rhythmfeatures of the human circadian biological clockpronunciation/sərˈkeɪdiən/ frequencyrepeats roughly every 24 hours the term circadian comes from the latin circa, meaning "approximately", and dies, meaning "day". processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (from german zeitgeber (german: ; lit. 'time giver')), which include light, temperature and redox cycles. in clinical settings, an abnormal circadian rhythm in humans is known as a circadian rhythm sleep disorder. history while there are multiple mentions of "natural body cycle" in eastern and native american cultures, the earliest recorded western account of a circadian process is credited to theophrastus, dating from the 4th century bc, probably provided to him by report of androsthenes, a ship's captain serving under alexander the great. in his book, 'περὶ φυτῶν ἱστορία', or 'enquiry into plants', theophrastus describes a "tree with many leaves like the rose, and that this closes at night, but opens at sunrise, and by noon is completely unfolded; and at evening again it closes by degrees and remains shut at night, and the natives say that it goes to sleep." the tree mentioned by him was much later identified as the tamarind tree by the botanist, h bretzl, in his book on the botanical findings of the alexandrian campaigns. the observation of a circadian or diurnal process in humans is mentioned in chinese medical texts dated to around the 13th century, including the noon and midnight manual and the mnemonic rhyme to aid in the selection of acu-points according to the diurnal cycle, the day of the month and the season of the year. in 1729, french scientist jean-jacques d'ortous de mairan conducted the first experiment designed to distinguish an endogenous clock from responses to daily stimuli. he noted that 24-hour patterns in the movement of the leaves of the plant mimosa pudica persisted, even when the plants were kept in constant darkness. in 1896, patrick and gilbert observed that during a prolonged period of sleep deprivation, sleepiness increases and decreases with a period of approximately 24 hours. in 1918, j.s. szymanski showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature. in the early 20th century, circadian rhythms were noticed in the rhythmic feeding times of bees. auguste forel, ingeborg beling, and oskar wahl conducted numerous experiments to determine whether this rhythm was attributable to an endogenous clock. the existence of circadian rhythm was independently discovered in fruit flies in 1935 by two german zoologists, hans kalmus and erwin bünning. in 1954, an important experiment reported by colin pittendrigh demonstrated that eclosion (the process of pupa turning into adult) in drosophila pseudoobscura was a circadian behaviour. he demonstrated that while temperature played a vital role in eclosion rhythm, the period of eclosion was delayed but not stopped when temperature was decreased. the term circadian was coined by franz halberg in 1959. according to halberg's original definition: the term "circadian" was derived from circa (about) and dies (day); it may serve to imply that certain physiologic periods are close to 24 hours, if not exactly that length. herein, "circadian" might be applied to all "24-hour" rhythms, whether or not their periods, individually or on the average, are different from 24 hours, longer or shorter, by a few minutes or hours. in 1977, the international committee on nomenclature of the international society for chronobiology formally adopted the definition: circadian: relating to biologic variations or rhythms with a frequency of 1 cycle in 24 ± 4 h; circa (about, approximately) and dies (day or 24 h). note: term describes rhythms with an about 24-h cycle length, whether they are frequency-synchronized with (acceptable) or are desynchronized or free-running from the local environmental time scale, with periods of slightly yet consistently different from 24-h. ron konopka and seymour benzer identified the first clock mutation in drosophila in 1971, naming the gene "period" (per) gene, the first discovered genetic determinant of behavioral rhythmicity. the per gene was isolated in 1984 by two teams of researchers. konopka, jeffrey hall, michael roshbash and their team showed that per locus is the centre of the circadian rhythm, and that loss of per stops circadian activity. at the same time, michael w. young's team reported similar effects of per, and that the gene covers 7.1-kilobase (kb) interval on the x chromosome and encodes a 4.5-kb poly(a)+ rna. they went on to discover the key genes and neurones in drosophila circadian system, for which hall, rosbash and young received the nobel prize in physiology or medicine 2017. joseph takahashi discovered the first mammalian circadian clock mutation (clockδ19) using mice in 1994. however, recent studies show that deletion of clock does not lead to a behavioral phenotype (the animals still have normal circadian rhythms), which questions its importance in rhythm generation. the first human clock mutation was identified in an extended utah family by chris jones, and genetically characterized by ying-hui fu and louis ptacek. affected individuals are extreme 'morning larks' with 4-hour advanced sleep and other rhythms. this form of familial advanced sleep phase syndrome is caused by a single amino acid change, s662➔g, in the human per2 protein. criteria to be called circadian, a biological rhythm must meet these three general criteria: the rhythm has an endogenous free-running period that lasts approximately 24 hours. the rhythm persists in constant conditions, i.e. constant darkness, with a period of about 24 hours. the period of the rhythm in constant conditions is called the free-running period and is denoted by the greek letter τ (tau). the rationale for this criterion is to distinguish circadian rhythms from simple responses to daily external cues. a rhythm cannot be said to be endogenous unless it has been tested and persists in conditions without external periodic input. in diurnal animals (active during daylight hours), in general τ is slightly greater than 24 hours, whereas, in nocturnal animals (active at night), in general τ is shorter than 24 hours. the rhythms are entrainable. the rhythm can be reset by exposure to external stimuli (such as light and heat), a process called entrainment. the external stimulus used to entrain a rhythm is called the zeitgeber, or "time giver". travel across time zones illustrates the ability of the human biological clock to adjust to the local time; a person will usually experience jet lag before entrainment of their circadian clock has brought it into sync with local time. the rhythms exhibit temperature compensation. in other words, they maintain circadian periodicity over a range of physiological temperatures. many organisms live at a broad range of temperatures, and differences in thermal energy will affect the kinetics of all molecular processes in their cell(s). in order to keep track of time, the organism's circadian clock must maintain roughly a 24-hour periodicity despite the changing kinetics, a property known as temperature compensation. the q10 temperature coefficient is a measure of this compensating effect. if the q10 coefficient remains approximately 1 as temperature increases, the rhythm is considered to be temperature-compensated. origin circadian rhythms allow organisms to anticipate and prepare for precise and regular environmental changes. they thus enable organisms to make better use of environmental resources (e.g. light and food) compared to those that cannot predict such availability. it has therefore been suggested that circadian rhythms put organisms at a selective advantage in evolutionary terms. however, rhythmicity appears to be as important in regulating and coordinating internal metabolic processes, as in coordinating with the environment. this is suggested by the maintenance (heritability) of circadian rhythms in fruit flies after several hundred generations in constant laboratory conditions, as well as in creatures in constant darkness in the wild, and by the experimental elimination of behavioral—but not physiological—circadian rhythms in quail. what drove circadian rhythms to evolve has been an enigmatic question. previous hypotheses emphasized that photosensitive proteins and circadian rhythms may have originated together in the earliest cells, with the purpose of protecting replicating dna from high levels of damaging ultraviolet radiation during the daytime. as a result, replication was relegated to the dark. however, evidence for this is lacking: in fact the simplest organisms with a circadian rhythm, the cyanobacteria, do the opposite of this: they divide more in the daytime. recent studies instead highlight the importance of co-evolution of redox proteins with circadian oscillators in all three domains of life following the great oxidation event approximately 2.3 billion years ago. the current view is that circadian changes in environmental oxygen levels and the production of reactive oxygen species (ros) in the presence of daylight are likely to have driven a need to evolve circadian rhythms to preempt, and therefore counteract, damaging redox reactions on a daily basis. the simplest known circadian clocks are bacterial circadian rhythms, exemplified by the prokaryote cyanobacteria. recent research has demonstrated that the circadian clock of synechococcus elongatus can be reconstituted in vitro with just the three proteins (kaia, kaib, kaic) of their central oscillator. this clock has been shown to sustain a 22-hour rhythm over several days upon the addition of atp. previous explanations of the prokaryotic circadian timekeeper were dependent upon a dna transcription/translation feedback mechanism. a defect in the human homologue of the drosophila "period" gene was identified as a cause of the sleep disorder fasps (familial advanced sleep phase syndrome), underscoring the conserved nature of the molecular circadian clock through evolution. many more genetic components of the biological clock are now known. their interactions result in an interlocked feedback loop of gene products resulting in periodic fluctuations that the cells of the body interpret as a specific time of the day. it is now known that the molecular circadian clock can function within a single cell. that is, it is cell-autonomous. this was shown by gene block in isolated mollusk basal retinal neurons (brns). at the same time, different cells may communicate with each other resulting in a synchronised output of electrical signaling. these may interface with endocrine glands of the brain to result in periodic release of hormones. the receptors for these hormones may be located far across the body and synchronise the peripheral clocks of various organs. thus, the information of the time of the day as relayed by the eyes travels to the clock in the brain, and, through that, clocks in the rest of the body may be synchronised. this is how the timing of, for example, sleep/wake, body temperature, thirst, and appetite are coordinately controlled by the biological clock. importance in animals circadian rhythmicity is present in the sleeping and feeding patterns of animals, including human beings. there are also clear patterns of core body temperature, brain wave activity, hormone production, cell regeneration, and other biological activities. in addition, photoperiodism, the physiological reaction of organisms to the length of day or night, is vital to both plants and animals, and the circadian system plays a role in the measurement and interpretation of day length. timely prediction of seasonal periods of weather conditions, food availability, or predator activity is crucial for survival of many species. although not the only parameter, the changing length of the photoperiod (day length) is the most predictive environmental cue for the seasonal timing of physiology and behavior, most notably for timing of migration, hibernation, and reproduction. effect of circadian disruption mutations or deletions of clock genes in mice have demonstrated the importance of body clocks to ensure the proper timing of cellular/metabolic events; clock-mutant mice are hyperphagic and obese, and have altered glucose metabolism. in mice, deletion of the rev-erba alpha clock gene can result in diet-induced obesity and changes the balance between glucose and lipid utilization, predisposing to diabetes. however, it is not clear whether there