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Our Biological Clocks

Help Link : Biological Clocks — Garden Variety Experiments Link : Oscillation

In 1997, U.S. neurobiologist Joseph Takahashi and his team identified a gene in mice which, when it mutates, lengthens their circadian period to 27 hours if they are kept in conditions of constant light. (After a few weeks under these conditions, many of the mutant mice even lose all periodicity in their behaviours.) A droll wit, Takahashi named this gene Clock, as an abbreviation for “circadian locomotor output cycles kaput”. This was the first gene ever identified as being involved in the circadian cycle of a mammal.

Link : First Circadian Clock Gene Identified And Cloned In Mammals Research : Biography of Joseph S. Takahashi

For several decades, scientists have known that the suprachiasmatic nuclei, two small groups of neurons in the hypothalamus, are necessary for the expression of the circadian rhythm in mammals. When the first genes in the biological clock of mammals were discovered in the late 1990s, the researchers therefore were not surprised to find that these genes were active in the neurons of the suprachiasmatic nuclei.

But the researchers also soon found that these same genes also displayed rhythmic activity in the cells of several other body tissues, and that this activity persisted for over a week when certain of these cells were isolated and grown in a culture medium in vitro.

Scientists now estimate that in total, somewhere between 8% and 15% of the genes in the human body operate on a cycle of about 24 hours.

Link : Peripheral Timekeeping: Mammalian Cells Outside The Brain Have Their Own Circadian Clocks Link : Peripheral "Swatch" Watches Are A Powerful Force In Body’s Circadian Rhythms

Every organism on Earth, including every human being, is the product of a long process of evolution. Ever since time began, this process has been influenced by the alternating pattern of day and night, caused by the rotation of the Earth itself.

Many human functions, such as alertness, body temperature, and the secretion of certain hormones, work better if they are adjusted according to whether it is day or night. As you might therefore expect, a mechanism has evolved within the human body to co-ordinate its major functions with the time of day.

The first scientific evidence of this “biological clock” came from studies in which volunteer subjects spent several weeks cut off from any cues as to whether it was day or night (often by camping in caves). The scientists running these studies found that even under these conditions, a cycle about 24 hours long persisted in both the behaviour and the physiology of these individuals.

Even when human cells are isolated in a culture medium in a laboratory and subjected to continuous light, they still display internal cyclical variations: the activity of certain genes and the secretion of certain substances continue to fluctuate in an approximately 24-hour pattern.

Thus the workings of the human biological clock reside right in our bodies’ cells. But instead of springs and gears, this clockwork is made out of molecules. Which molecules, and how they interact to maintain 24-hour cycles, are complex questions. Scientists did not even begin to answer them until the early 1970s, when the first genes involved in the biological clock were discovered in the fruit fly, Drosophila.

History Module: How Biological Clock Genes Were First Discovered in Fruit Flies Link : What Mutant Flies Reveal

The true complexity of these questions became apparent, however, when scientists realized that every species has some features in its biological clock that are unique to that species. For example, our human biological clock includes some molecules that are the same as in the fruit fly’s, but others that are specific to humans. The underlying mechanism in all cases, however, is a cycle commonly known as a negative feedback loop.

Tool Module : Cybernetics

This cycle starts with genes–segments of DNA in the nucleus of each cell–that provide the instructions for manufacturing proteins. These instructions are carried by a molecule called messenger RNA (mRNA) from the genes to the cytoplasm (cell body), where the proteins are actually produced. Most proteins then remain in the cytoplasm, where they perform various functions (they are sometimes known as the “building blocks of life”). But the proteins involved in the human biological clock instead enter the cell’s nucleus and bind to the genes that caused them to be produced. By doing so, these proteins halt the activity of their own genes, so that the cell starts manufacturing less of these proteins. Eventually, however, the quantity of proteins being manufactured in the cytoplasm and entering the nucleus decreases so much that it no longer suffices to suppress protein production. Protein production then resumes and the proteins begin building up again, thus initiating the next new cycle. This entire process takes about 24 hours.

Adapted from: Howard Hughes Medical Institute

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