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.
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.
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.
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.
