The discovery of the circadian photoreceptor - Assignment Example

Biology Assignment Question Describe the discovery of the circadian photoreceptor (the cell and the molecule). The conceptualization of circadian photoreceptor molecules began it around 19th century when documentation of the plant response to the blue light accrued. However, the real effect of the rhythmic cycles could not be offer enough evidence since the experiments conducted were challenging to adapt to these changes. Therefore, it was not until early 1900s that a genetic perspective proved helpful in trying to understand the behavior of these photoreceptor molecules (Martha , Spoelstra and Roenneberg, 930). The gene coding for these photoreceptors were detected by breeding of bean plant under two different conditions, of long periods and short periods. Unfortunately, the light and dark periods were not considered, therefore the experiment would prove disastrous to deal with especially in conducting the genetic analysis. Following a long struggle over many decades’ scientists in due course were able to detect some of the genes responsible for coding of these circadian rhythmic proteins. At around 1970s, the knowledge of mutagenesis would act as the focal point to the first discovery of these genes, which later would attain the name ‘clock genes’ in the Drosophila melanogaster fly (Nicolas and Sassone-Corsi, 59).This improved the prospects of the eventual discovery of the photoreceptor cells and their molecular make up. Later on, there was an increase in the discovery of many other genes coding for the circadian rhythm from several plant as well as animal families (Nicolas and Sassone-Corsi, 59). At around 1980s, scientists discovered a gene called HY4 that they thought was solely responsible for the blue light detection in Arabidopsis thaliana plant (Nicolas and Sassone-Corsi, 60). More experiments conducted found out its homology in mammals and their effects attributed to the functions of photolyases. Further research proved that the HY4 gene was a different photo-pigment gene in one of the Arabidopsis thaliana loci that did code for blue-light sensitivity but did not affect the photolyases production (Martha , Spoelstra and Roenneberg, 932). However, these experiments proved crucial in the mid-1990s to the discovery of a new molecule known as the Cryptochrome that showed a close relation to photolyases in the bacteria cells (Nicolas and Sassone-Corsi, 60). Cryptochrome genes cry1 and cry2 coded for universal proteins, CRY 1 and CRY 2 found in almost all the kingdoms of the living organisms (Nicolas and Sassone-Corsi, 60). These proteins activated the light sensitive cofactors and cells that make the photoreceptor cells to detect light in rhythmic manner. They also act as DNA repair enzymes in case of any damage from light related radiations such as the UV light (Robert , Lucas et al, 505). The unearthing of the molecules would then give clue to the discovery of the cells of the circadian photoreceptors. Consequently, this followed the exhumation of most of the photoreceptive cells that respond to the 24- hour clock in the first quarter of 1900s (Martha , Spoelstra and Roenneberg, 931). These special cells, found to be containing a pigment known as melanopsin, would later acquire different names including intrinsically photosensitive Retinal Ganglion Cells (ipRGC) (Howard, Herbin and Nevo, 156). This was many decades later after the discovery of the rods and cons in the mammalian eye, making the ipRGC a new element at the time. Much of the changes in the findings into these cells did not accrue until around the year 1990s, the same time that research on the circadian molecules was very active. However slow in their activities, they were solely responsible for the change in the rhythmic day and light cycles (Martha , Spoelstra and Roenneberg, 932). In addition, the pigments have recently been active even without the presence of cones and rods thereby helping the individual to detect the slightest changes of light and darkness. Actually, the detection of this ability for the first time was in 1991, when the scientist discovered the photoreceptor cells in mice that could function without the support of the cones and the rods; they virtually depended on the photoreceptive abilities of melanopsin. In fact, additional research in the 21st century would reveal that the melanopsin is the only photoreceptor pigment in the circadian active ganglion cells. Question 2- Describe the important candidates that were proposed to be circadian photoreceptors, show how these were proven not to be the circadian photoreceptor, and discuss how the true photoreceptor was discovered. The discovery towards circadian photoreceptor proved to be challenging and deceptive over a long period. Scientists would stumble at many molecules and pigments such as the HY4 genes and the cones and rods before coming into the right conclusions (Martha , Spoelstra and Roenneberg, 933). Earlier on, the cones and rods were thought to be the only cells in control for the photo-transduction in the retina of the eye. This led to their incrimination as the cells that were also responsible for the rhythmic dark and light cycles. However, the incrimination would prove to the contrary after the discovery of this new class of the ganglion cells. At first, the histological functionality of the cones and rods was so clear that its contribution to the circadian cycles was undisputed. The discovery of opsonins, the protein that regulated photo-pigment transduction in these cells deceived the scientist even further. This protein, otherwise known as rhodopsin in the rods and photopsins in the cones, contained a pigment called retinal that was responsible for the transduction of light/dark signals from the environment to a signal that could be viable to the brain. All these photocells and their pigments were present in the innermost parts of the retina of the eye. Therefore, all the reflexes between the brain and the pupil, the regulation of light and dark cycles and the control of other entities that the eye could detect apart from the visual receptions, would be part of the misconception that these cells were in charge. Supplementary research into this aspect would later save the situation after a new pigment evidenced to be solely in charge of the circadian photoreception. This was the discovery of the retinal ganglion cells (RGCs) within the inner parts of the retinal cells (Howard, Herbin and Nevo, 156). A major prove came when the cones and rods of the mice used in the experiment were extracted and still the animal could still detect the rhythmic 24-hour light and darkness (Chalupa and Williams, 67). This led to a deeper investigation to find out, which type of pigments it possessed if not the opsonins found in the cones and rods that could be responsible for the signal transduction to the brain. As a result, anew pigment called the melanopsin found in these retinal ganglion cells exclusively attested as the main circadian pigment. The focus on the Cryptochrome as the main photo-pigment gradually shifted to the melanopsin, which was extant in other parts of the mammalian body (Martha , Spoelstra and Roenneberg, 933). In humans, the detection of the pigment was visible only in the retinal cells, evidence that would prove the earlier misconception of the opsonins also found in the retinal cells as the circadian photo-pigments. The exhumation of this new photo-pigment came from the novel idea of scientists who wanted to investigate the interactions between the photo-pigment cells and the suprachiasmatic nucleus (SCN) of the hypothalamus (Martha , Spoelstra and Roenneberg, 933). The SCN acts the pacemaker for rhythmic circadian cycle but is unable to entrain or synchronize it. A different mechanism is therefore, required to control the cycle to conform with the normal 24- hour clock light/ darkness fluctuations. At around 1980s, the synchronization exhibited high thresholds that the scientist started to question the full responsibility of cones and rods (Howard, Herbin and Nevo, 158). They found out that the signal innervation between the SCN and the eyes continued even with the complete removal of the cones and rods in mammals and even in blind humans (Howard, Herbin and Nevo, 158). This would lead the scientist to come up with the new sensitive photo-pigment cells the referred to as intrinsically photosensitive Retinal Ganglion Cells (ipRGC). Question 3- How do the functional properties of the true circadian photoreceptor make it useful for light input to the clock. The structural and functional property of the circadian photoreceptor (ipRGC) is a fundamental tool to its adaptability to the control of the rhythmic light and darkness. In human beings, the photoreceptor is calculatedly located at the inner parts of the retinal ganglion cells whereas the cones and rods reside in the outer parts. Here they are small ratio as compared to the rest of the pigments yet are very difficult to reach. For instance, a strong radiation may destroy the opsonins of the rods and cones but the melanopsin will remain undisrupted. They only consist of about 3% of the total ganglion cell, but have been exempted from other function of the pigments like image depiction, in order to concentrate on the signal transduction (Howard, Herbin and Nevo, 156). However, they seem to be a bit slow in their sensitivity towards light as compared to the rest of the photoreceptor pigments like the opsonins. Fortunately, this may be an added advantage since with the sluggish reaction and short latent period, they can also retain the information for long and in case of destructive radiation, and they are not easily affected (Robert , Lucas et al, 505). The distribution of circadian photoreceptor in the bodies of other organisms is not trivial to ignore relating to its accurate in put to the clock. In other mammals like the frog, the melanopsin is detectible even on the legs of these animals (Howard, Herbin and Nevo, 158). This would mean that even under hibernation when both the cones and the rods are not in function the pigment on the skin would be in full function to depict the changes in their environment. Still as mentioned in other animals the pigment is widely spread on their body tissues, the skin being a major harbour of these photoreceptors (Chalupa and Williams, 71). The mechanism of signal relay of these photoreceptor acts as the core to their function as the circadian entrains. They are less sensitive to light as compares to the cones and rods, but with this, they still relay the signal devotedly to the brain. The brain happens to be their output where all their signals are transduced which is contrary to the retina acting as the output for cones and rods. As the light intensity increases, the circadian photoreceptor depolarizes which in totally opposite to the hyperpolarization witnessed in the case of the cones and rods. Nevertheless, even with the depolarization effect they could still maintain their photo-transduction effect, making them unique among other receptor in the RCGs. The wavelength sensitive region of these circadian photoreceptors are almost the same as those of the cones and the rods, since they share the same wavelength as that of vitamin-A photo-pigments (Robert , Lucas et al, 506). This scenario could however, be contradicted in the case of their wavelength requirements in rats. An experiment conducted using rats revealed that the ipRCGs were more sensitive at a wavelength of ~484nm, the rods at ~500nm and the cones either between ~519nm and 359nm (Robert , Lucas et al, 505). This would suggest that there is the presence of classical photoreceptors that would entrain the clock in case of absence of cods and rods. It also would give the clue to the effect of light in terms of the photoreaction and sensitivity of these circadian photoreceptors (Robert , Lucas et al, 506). The circadian send their signal to the mid-brain, which acts as their output and therefore control other photo-related activities as well. The release of melatonin hormone from the pineal gland used to control photic regulation is evidently its sole function (Robert , Lucas et al, 505). They also control the actions of the pupil by their minute connections to the nerves in the retina. This would suggest their intrinsic value to the function of the eye as well as the control of the rhythmic clock (Robert , Lucas et al, 505). Works Cited Chalupa, Leo M., and Robert W. Williams. Eye, retina, and visual system of the mouse. Cambridge, Mass.: MIT Press, 2008. Print. Howard, Cooper M, Marc Herbin and Eviator Nevo. "Ocular Regressions Conceals Adaptive Progression of the Visual System in a Blind Subterranean Mammal." NATURE (1993): 156-159. Martha , Merrow, Kamiel Spoelstra and Till Roenneberg. "The Circadian Cycle: Daily Rhythms from Behaviour to Genes." European Molecular Biology Association (2005): 930-935. Nicolas , Cermakian and Paolo Sassone-Corsi. "Multilevel Regulation of Circadian Clock." NATURE REVIEWS: Molecular Cell Biology (2000): 59-67. Robert , J, Lucas and et al. "Regulation of the Mammalian Pineal by Non-rod,Non-cone, Ocular Photoreceptors." SCIENCE (1999): 504-507. Read More