The 2017 award of the Nobel Prize in physiology and medicine to three Americans, Michael Rosbash, Jeffrey Hall and Michael Young, has served to stimulate our interest in a phenomenon that is actually well-known. We all know why people get hungry about the same time of day, or wake up about the same time, or suffer from jet-lag. It is because of biological clocks. So what was so special about the work of these three scientists? The story actually goes back to 1729!
It was in the eighteenth century that French physicist and mathematician Jean Jacques d’Ortous de Mairan turned his attention to the mimosa plant. The leaflets making up each leaf of this plant, characteristically open outward in the daytime and fold inward at night. He had supposed that the plant reacted this way in response to the onset of day or night. However when he placed the plant in a dark cupboard, it continued to open and close its leaves at the appropriate time of day even when there was no light. He did not know why.
Much later, in the 1930s, Dr. Erwin Bunning of Germany began a 50 year program on such organisms as the common bean plant. Dr. Bunning’s work provided a clear demonstration that there is an internal clock. Another scientist discovered that the time of emergence of adult fruit flies (from pupae) also exhibited a close, but not exact daily rhythm. Scientists then developed a definition of circadian rhythms. (Circa is Latin for “approximately”, and diem is Latin for “day”, so circadian means “about a day”.)
These cycles are independently controlled inside the creature and follow a close, but not exact 24 hour cycle. This cycle is typically reset each morning with sunrise to follow an exact 24 hour cycle. While most chemical reactions including physiological processes double their rate with each 10 degree C rise in temperature, circadian rhythms are not affected by temperature. This is a very good thing. Imagine if your daily rhythms changed with the ambient temperature!
The search was then on to find out how many organisms exhibit biological clocks. Scientists had thought that some kinds of organism might lack this capacity, but the 1998 discovery of a clear circadian rhythm in blue-green algae (cyanobacteria) demonstrated to them that basically all organisms exhibit a biological clock.
Another thing that scientists wanted to discover was where the clock is located in each organism. It was in fruit flies that Ronald Konopka and Seymour Benzer demonstrated in 1971 that a gene which they called period was involved in control of the time of emergence of the adult fly from its pupa. Also James Truman and Lynn Riddiford, using silk moths (which are much bigger than fruit flies!), were able to demonstrate a light receptor, a clock, and hormonal and nervous output from special cells in the brain which control the daily rhythm of emergence of individuals from the pupal state.
Now scientists wanted to discover how the system works. The team of Konopka and Benzer had begun this stream of research in the 1970s, but they died in 2015 and 2007 respectively. The Nobel Prize is awarded only to people who are living and Hall, Young and Rosbash, from two competing teams, further elucidated the chemical process in fruit flies. This was the beginning of an explosion of similar studies in many other organisms.
The details of the physiology can be illustrated as follows. Imagine that you own a very valuable document. It contains specific recipes for all sorts of valuable products. Naturally you do not want to lose or damage that document. When you desire a given product, you make a copy of the appropriate piece of text and bring that copy to your manufacturing centre. Obviously, you need to locate the correct piece of information before you can make a copy. It would be ideal to have a marking system that hones in on the correct piece of information, especially if the total document is many volumes thick. Without a marking device, you will never find the correct recipe.
So it is with the living cell. Consider the nucleus as the information centre of the cell. To produce a needed molecule for the cell, a special marker protein attaches at just the right spot to the information bearing DNA. Then comes a different protein (polymerase) to the marker point, and the polymerase then proceeds along the crucial stretch of DNA, copying the information into another long molecule. The polymerase cannot find the right piece of DNA without the marker. The duplicating process is like something skimming along a line of text on a page and duplicating the order of letters in the words at the same time.
Next that piece of duplicated information (like ticker tape), then exits the nucleus into the surrounding part of the cell (called cytoplasm). There the duplicated piece of information chugs through a tiny machine and directs the production of the desired product (also a protein). But once that protein product is used in the cell, the system has to be repeated from the beginning to make more useful protein. It is just like spending money and earning more so that you can keep on spending.
One particularly interesting variation on the just described process involves timekeeping in living organisms. Fruit flies provide an excellent example of the situation. In certain cells of the fruit fly brain, a gene called Period directs the production of a protein labelled PER. Another gene Timeless directs the production of TIM. Both proteins are formed outside the nucleus in the cytoplasm. During the day these processes continue and more and more of these proteins accumulate in the cell proper (cytoplasm). Then as night falls, individual PER and TIM proteins link together and move through very particular gates in the nuclear membrane into the central nucleus. There they tie up the special marker proteins which attach at the beginning of the DNA where these genes are located. Thus production of PER and TIM stops. The process continues through the night so that by morning there is almost no PER and TIM left. When there is nothing left to prevent the expression of the Period and Timeless genes, these genes are then turned on again and the cycle repeats. This is a simple feedback loop which controls a number of other physiological processes in the fruit fly such as time of mating and time of day for an adult fly to emerge from the pupa.
The biological clock therefore is basically a feedback system, or a simple loop. A gene directs the production of a protein which then slows down the action of that gene. Eventually other proteins were discovered which also affect the system. Each has its own feedback system which interacts with neighbouring loops. Expert John Tyler Bonner declared in 2004: “It became evident that the clock was controlled by a complex network of genes and their proteins; and that this was the mechanism that provided the underlying oscillations.”
Scientists had hoped, based on evolution theory, that a common mechanism would be found in all organisms. Dr. Bonner however declared concerning genes that control daily rhythms in different major groups of organisms: “They are similar in the way they behave and function, but they involve different DNAs and different proteins.” This expert tried to accommodate the situation to evolution theory: “It may at first glance seem unlikely that such genes should appear spontaneously, but it is worth bearing in mind that they had many millions of years and many millions of generations for this fortuitous arrangement to occur.” (This is not a promising argument!)
The discovery of a circadian rhythm in blue-green algae (cyanobacteria) in 1998 settled the question of whether there was one common mechanism in organisms or many. Commentary in Science (vol. 281 September 4/98 p. 1429) points out that although the new system is similar “the proteins that make up the cyanobacteria clock are completely different from those of other organisms.” Commentator Marcia Barinaga continues: “The findings help settle a debate over whether all biological clocks are descended from the same evolutionary ancestor, or whether clocks have arisen more than once during the course of evolution.” And she concludes: “[C]locks seem to have arisen multiple times, recreating the same design each time.”
Thus the claim to fame of the new Nobel laureates is that they were among the pioneers in the discovery of molecular controls of biological clocks. These processes produce truly amazing results such as the Monarch Butterfly migration (www.create.ab.ca/monarch-butterflies-special-orienteers/). These butterfly clocks themselves include some unique components. We now know how amazing are the capabilities which organisms demonstrate, which are controlled by biological clocks. We also realize that biological clocks are a big problem for evolution theory. This wonderful system, with all its diverse chemical differences, was clearly designed by the Creator.
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