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Convergent latitudinal erosion of circadian systems in a rapidly diversifying order of fishes.

Biological clocks allow organisms to anticipate cyclical environmental changes, yet in high-latitude or deep-sea habitats, the diel cues that entrain these rhythms are often seasonally diminished or absent. Fishes of the order Perciformes have rapidly diversified across these arrhythmic ecosystems, raising the question of whether changes to circadian rhythms and biological clock genetic architecture are a component of their evolutionary success. Here, we used a comparative genomic approach to investigate patterns of core biological clock gene loss across 96 perciform and five outgroup species. We found widespread and lineage-specific loss in core clock genes, particularly in the convergently evolving polar and deep-sea suborders Notothenioidei and Cottoidei. This trend of clock gene loss was significantly amplified with higher-latitude species. To determine if these genomic signatures reflect a functional loss of rhythmicity, we performed metabolic phenotyping on three notothenioid species. We found a consistent lack of circadian metabolic oscillations during the late austral fall across all notothenioids, including the sub-Antarctic sister lineage to the cryonotothenioid adaptive radiation, Eleginops maclovinus. Experimental data across Perciformes, combined with suborder-wide patterns of gene loss, suggest that a release from circadian constraints occurred early in their diversification, potentially facilitating the repeated expansion of these fishes into polar and deep-sea habitats.

Animals↗

Measurement of time in oligodendrocyte-type-2 astrocyte (O-2A) progenitors is a cellular process distinct from differentiation or division.

When stimulated by platelet-derived growth factor (PDGF), oligodendrocyte-type-2 astrocyte (O-2A) progenitors derived from perinatal rat optic nerves undergo a limited number of cell divisions before clonally related cells synchronously and symmetrically differentiate into nondividing oligodendrocytes. The duration of this mitotic period is thought to be controlled by a cell-intrinsic biological clock. Thus, in the presence of PDGF, the measurement of time by the biological clock is intimately coupled to the control of division and differentiation. In contrast, O-2A progenitors grown in the presence of PDGF plus basic fibroblast growth factor (bFGF) divide indefinitely in the absence of differentiation and so do not exhibit a limited period of division. We have tested whether growth in PDGF plus bFGF alters the duration of the limited period of division O-2A progenitors exhibit in response to PDGF alone. Accordingly, O-2A progenitors were grown in the presence of PDGF plus bFGF for varying lengths of time, before being switched to conditions that promote timed differentiation (PDGF but not bFGF). Increasing duration of culture in PDGF plus bFGF led to a gradual shortening of the period for which O-2A progenitors were subsequently responsive to PDGF alone, until eventually all cells differentiated without dividing after switching. In contrast, a short exposure to bFGF was not sufficient to cause a similar alteration in the pattern of differentiation. These results indicate that O-2A progenitors prevented from undergoing timed differentiation nevertheless retain the ability to measure elapsed time, implying that the biological clock in this cell type can be uncoupled from differentiation. Furthermore, they demonstrate that the biological clock does not impose an absolute limit on the number of divisions that an O-2A progenitor can undergo. In contrast with existing hypotheses, our observations suggest that the molecular mechanism that controls timed differentiation must consist of at least two components, with the clock itself being in some manner distinct from mechanisms that limit cell division and/or directly regulate differentiation.

Animals↗

The circadian E-box: when perfect is not good enough.

Life on earth has evolved on a photic carousel, spinning through alternating periods of light and darkness. This playful image belies the fact that only those organisms that learned how to benefit from the recurring features in their environment were allowed to ride on. This selection process has engendered many daily rhythms in our biosphere, most of which rely on the anticipatory power of an endogenously generated marker of phase: the biological clock. The basic mechanisms driving this remarkable device have been really tough to decode but are finally beginning to unravel as chronobiologists probe deeper and wider in and around the recently discovered gears of the clock. Like its chemical predecessors, biological circadian oscillators are characterized by interlaced positive and negative feedback loops, but with constants and variables carefully balanced to achieve an approximately 24h period. The loops at the heart of these biological oscillators are sustained by specific patterns of gene expression and precisely tuned posttranscriptional modifications. It follows that a molecular understanding of the biological clock hinges, in no small measure, on a better understanding of the cis-acting elements that bestow a given gene with its circadian properties. The present review summarizes what is known about these elements and what remains to be elucidated.

Animals↗

Photoperiodic regulation of seasonal breeding in birds.

Day length-dependent breeding in birds commonly occurs in spring and summer, but may occur after exposure to complex changes in day length, as for example in transequatorial migrants. More rarely, some photoperiodic birds breed when day lengths are decreasing or are short. The flexibility of avian photoperiodic breeding strategies may reflect modifications to a common reproductive photoperiodic neuroendocrine system. This involves an extraretinal photoreceptor and a biological clock, which generates a circadian rhythm of photoinducibility to measure photoperiodic time. The pineal gland is not essential for the reproductive photoperiodic response. The current model of the avian photoperiodic response has been modified to accommodate short day breeders, by incorporating a role for seasonal changes in prolactin secretion in the termination of breeding. Analysis of the sites of expression of clock genes suggests that the biological clock for reproductive photoperiodic time measurement is in the medial basal hypothalamus. Photoperiodic signal transduction may involve a clock-dependent local conversion of thyroxine to triiodothyronine (T(3)) in the medial basal hypothalamus mediated by increased expression of the gene encoding type 2 iodothyronine deiodinase. This photoinduced increase in T(3) may stimulate the release of gonadotrophin-releasing hormone (GnRH) through thyroid hormone receptors in the median eminence. These may mediate retraction of glial cell end-feet ensheathing GnRH nerve terminals abutting onto the hypophysial portal vasculature, allowing GnRH to be released to stimulate gonadotrophin secretion.

Animals↗

Interaction between the circadian clocks of mother and fetus.

In mammals, a unidirectional communication exists between the biological clocks of the mother and fetus. As a biological clock begins oscillating in the suprachiasmatic nuclei of the fetus, redundant circadian signals entrain the fetal clock to the prevailing light-dark cycle. Recent studies have revealed an activatable dopamine system within the fetal hypothalamus which may serve as a final common pathway by which maternal signals entrain the fetus. An entrained biological clock during fetal life makes the developing mammal better prepared for life in the outside world.

Animals↗

Regulation of output from the plant circadian clock.

Plants, like many other organisms, have endogenous biological clocks that enable them to organize their physiological, metabolic and developmental processes so that they occur at optimal times. The best studied of these biological clocks are the circadian systems that regulate daily (approximately 24 h) rhythms. At the core of the circadian system in every organism are oscillators responsible for generating circadian rhythms. These oscillators can be entrained (set) by cues from the environment, such as daily changes in light and temperature. Completing the circadian clock model are the output pathways that provide a link between the oscillator and the various biological processes whose rhythms it controls. Over the past few years there has been a tremendous increase in our understanding of the mechanisms of the oscillator and entrainment pathways in plants and many useful reviews on the subject. In this review we focus on the output pathways by which the oscillator regulates rhythmic plant processes. In the first part of the review we describe the role of the circadian system in regulation at all stages of a plant's development, from germination and growth to reproductive development as well as in multiple cellular processes. Indeed, the importance of a circadian clock for plants can be gauged by the fact that so many facets of plant development are under its control. In the second part of the review we describe what is known about the mechanisms by which the circadian system regulates these output processes.

Arabidopsis↗

Adaptive significance of a circadian clock: temporal segregation of activities reduces intrinsic competitive inferiority in Drosophila parasitoids.

Most organisms show self-sustained circadian oscillations or biological clocks which control their daily fluctuations in behavioural and physiological activities. While extensive progress has been made in understanding the molecular mechanisms of biological clocks, there have been few clear demonstrations of the fitness value of endogenous rhythms. This study investigated the adaptive significance of circadian rhythms in a Drosophila parasitoid community. The activity rhythms of three sympatric Drosophila parasitoids are out of phase, the competitively inferior parasitoid species being active earlier than the superior competitor. This temporal segregation appears at least partially determined by endogenous periods of the clock which also vary between species and which correlate the time of activity. This earlier activity of the inferior competitor significantly reduces its intrinsic competitive disadvantage when multiparasitism occurs, thus suggesting that natural selection acting on the phase of the rhythm could substantially deviate the endogenous period from the optimal ca. 24 h period. This study demonstrates that temporal segregation of competing species could be endogenously controlled, which undoubtedly favours their coexistence in nature and also shows how natural selection can act on biological clocks to shape daily activity patterns.

Adaptation, Physiological↗

All in good time: the Arabidopsis circadian clock.

Biological time-keeping mechanisms have fascinated researchers since the movement of leaves with a daily rhythm was first described >270 years ago. The circadian clock confers a approximately 24-hour rhythm on a range of processes including leaf movements and the expression of some genes. Molecular mechanisms and components underlying clock function have been described in recent years for several animal and prokaryotic organisms, and those of plants are beginning to be characterized. The emerging model of the Arabidopsis clock has mechanistic parallels with the clocks of other model organisms, which consist of positive and negative feedback loops, but the molecular components appear to be unique to plants.

Animals↗

[Cellular mechanisms of circadian clocks].

The mechanisms of the biological clock are today being investigated in single neurons in cell culture or in unicellular and in other microorganisms. The results show that all components of this "endogenous clock" can be found at the cellular level. The cellular circadian program is controlled by a complex system of biochemical reactions, which can contain more than one circadian pacemaker and which comprises several feed-back loops at the input and the output side. This complex temporal program is a prerequisite for specialization and survival within the chrono-ecological niches of the "temporal space" day. It enables organisms on the one hand to adaptively react to environmental changes and thereby reaching transient independence of the external, physical time course; on the other side, it ensures that the endogenous day never runs out of synchrony with the solar day of the environment.

Animals↗

Bilirubin, REM sleep, and phototransduction of environmental time cues. A hypothesis.

The prevailing hypothesis for phototransduction is that visual (rod or cone) pigments mediate light's primary effects on biological clock systems. Common light-responsive chronobiological behavioral properties of plants and animals and some common molecular structures of plants and animals suggest the possibility that heme moieties and bile pigments in animals mediate some nonvisual influences of light on neuroactive gases and biological rhythms. As plant phytochrome resets the plant biological clock, the similar chromophore in bile pigments is proposed to transduce environmental light zeitgeber signals to endogenous biological clocks. The temporal association of plasma bilirubin and rapid-eye-movement (REM) sleep in populations, the correlation of secretion of biliary bilirubin with REM sleep among 10 different species (Spearman r = 0.89, p < 0.002), and the known responses of bilirubin to light lead to the hypothesis that bilirubin, in particular, plays an evolutionary role in the regulation of REM sleep and in mediating some of light's antidepressant effects.

Animals↗

Long-lived alphaMUPA transgenic mice exhibit pronounced circadian rhythms.

Robust biological rhythms have been shown to affect life span. Biological clocks can be entrained by two feeding regimens, restricted feeding (RF) and caloric restriction (CR). RF restricts the time of food availability, whereas CR restricts the amount of calories with temporal food consumption. CR is known to retard aging and extend life span of animals via yet-unknown pathways. We hypothesize that resetting the biological clock could be one possible mechanism by which CR extends life span. Because it is experimentally difficult to uncouple calorie reduction from temporal food consumption, we took advantage of the murine urokinase-like plasminogen activator (alphaMUPA) transgenic mice overexpressing a serine protease implicated in brain development and plasticity; they exhibit spontaneously reduced eating and increased life span. Quantitative real-time PCR analysis revealed that alphaMUPA mice exhibit robust expression of the clock genes mPer1, mPer2, mClock, and mCry1 but not mBmal1 in the liver. We also found changes in the circadian amplitude and/or phase of clock-controlled output systems, such as feeding behavior, body temperature, and enteric cryptdin expression. A change in the light-dark regimen led to modified clock gene expression and abrogated circadian patterns of food intake in wild-type (WT) and alphaMUPA mice. Consequently, food consumption of WT mice increased, whereas that of alphaMUPA mice remained the same, indicating that reduced food intake occurs upstream and independently of the biological clock. Thus we surmise that CR could lead to pronounced and synchronized biological rhythms. Because the biological clock controls mitochondrial, hormonal, and physiological parameters, system synchronicity could lead to extended life span.

ARNTL Transcription Factors↗

Circadian biology: fibroblast clocks keep ticking.

Real-time cellular imaging of gene expression has revealed that fibroblasts contain a robust, self-sustained and cell-autonomous circadian oscillator, with a range of properties that both overlap and contrast with those of the neural clock of the suprachiasmatic nuclei.

Animals↗

[How many pieces to build a circadian clock?].

Biological rhythms represent a fundamental property of various living organisms. In particular, circadian rhythms, i.e. rhythms with a period close to 24 hours, help organisms to adapt to environmental daily rhythms. Although various factors can entrain or reset rhythms, they persist even in the absence of external timing cue, showing that their generation is endogenous. Indeed, the suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be the main circadian clock in mammals. Isolated SCN neurons have been shown to display circadian rhythms, and in each cell, a set of genes, called "clock genes", are devoted to the generation and regulation of rhythms. Recently, it has become obvious that the clock located in the SCN is not homogenous, but is rather composed of multiple functional components somewhat reminiscent of its neurochemical organization. The significance and implications of these findings are still poorly understood but pave the way for future exciting studies. Here, current knowledge concerning these distinct neuronal populations and the ways through which synchronization could be achieved, as well as the potential role of neuropeptides in both photic and non-photic resetting of the clock, are summarized. Finally, we discuss the role of the SCN within the circadian system, which also includes oscillators located in various tissues and cell types.

Animals↗

Genetic clock of biologic rhythms.

Biologic rhythms are tightly regulated in all species, in order to adapt to circadian variations of light, temperature and other biological related living conditions. The intrinsic mechanisms of rhythm regulation from every cell to a whole organism is embedded into the genetic clockwork. The mammalian clock genes are reviewed with their interrelation. The per gene promoter is stimulated by clock/bmal1 heterodimer and trigger the per proteins synthesis. Initially considered as a simple negative feed-back, from to the phosphorylated per/cry heterodimer towards clock/bmal1 transcription stimulus, the clockweb of the cell became complex. General characteristics of cell clock genes are integrated in a model. In addition, the involvement of clock genes in peripheral tissues is discussed.

Animals↗

Slow oscillation circuit of the intergeniculate leaflet.

The slow oscillation circuit of the intergeniculate leaflet seems to constitute a natural basic rhythm of the neuronal mechanism of mammalian biological clock. The results of studies conducted so far indicate that photic information flowing from ganglion cells of the retina is necessary for its generation. On the other hand, this circuit is maintained thanks to the oscillatory activity of GABAergic interneurons, the majority of which build up this structure, mainly in combination with neuropeptide Y and enkephalins. The activity of non-specific projections of the brain, whose terminals are present in the intergeniculate leaflet, modulates the slow oscillation circuit of the leaflet neurons, without changing its oscillatory pattern, though. Our hypothesis predicts a role of the oscillatory activity of intergeniculate leaflet neurons in facilitation the secretion of neuropeptides and neurohormones present in the very elements making up the mechanism of mammalian biological clock and structures linked to it. This constitutes a kind of functional junction between the central mechanism of mammalian biological clock with an ultradian rhythm and its peripheral clocks whose rhythm is circadian.

Animals↗

Expression of clock gene in the brain of rainbow trout: comparison with the distribution of melatonin receptors.

To identify brain structures potentially acting as biological clocks in rainbow trout (Oncorhynchus mykiss), the expression sites of a trout homolog of the mouse clock gene were studied and compared with that of melatonin receptors (Mel-R). For this purpose, a partial sequence of the trout clock gene, including a PAS domain, was obtained by reverse transcription-polymerase chain reaction and used to perform in situ hybridization. The highest density of clock transcripts was observed in the periventricular layer (SPV) of the optic tectum, but a weaker expression was detected in some pretectal nuclei, such as the posterior pretectal nucleus (PO) and the periventricular regions of the diencephalon. Comparison of the hybridization signal in fish sacrificed at 08:00 and 17:00 did not indicate major changes in clock expression levels. Comparison of adjacent sections alternatively treated with clock and Mel-R probes suggests that both messengers are probably expressed in the same cells in the SPV and PO. In addition, in situ hybridization with a glutamate decarboxylase 65 probe, demonstrates that cells expressing clock and Mel-R in the optic tectum are gamma-aminobutyric acid neurons. The tight overlapping between the expression of Mel-R and clock transcripts in cells of the PO and SPV suggests a functional link between these two factors. These results indicate that the optic tectum and the pretectal area of the rainbow trout are major sites of integration of the melatonin signal, express the clock gene, and may act as biological clocks to influence behavioral and endocrine responses in trout.

Amino Acid Sequence↗