SCIENTISTS in the US have isolated a gene that controls the biological clock in mice. With this, they have moved closer to
understanding the cause of a
host of human ailments, 'from
jet lag to sleep disorders related to aging, to manic depressive illness. Joseph S Takahashi and colleagues from North-western University, have for
the first time identified the
clock gene' in mammals. The
discovery is a major step
towards unlocking the mysteries of biological clocks, which are an
aggregation of cells that control the
daily lives of everything from microbes to man.
"There is every reason to expect that
it will inform us about how the human
clock works, though practical applications are still a long way off," says
Charles J Weitz, a molecular neurobiologist at Harvard Medical School. The
biological clocks in most plants and animals work on roughly a 24-hour basis.
In humans, the cyclic fluctuations of the
clock known as circadian rhythms, govern rhythms like the sleep-wake cycle,
metabolic rate, hormone levels, body
temperature and the variations in mental alertness. The clock resets itself daily according to the amount of light perceived, and a poorly-adjusted body clock can over a period of time lead to
various sleep disorders.
In mammals, the clock is located in
a deep central structure in the brain
called the hypothalamus, just above the
point at which the optic nerves from
each eye cross in mid-brain. The hypothalamus contains the suprachiasmatic
nucleus, which consists of some 10,000
nerve cells, each containing a tiny clock
at the level of its genes and proteins.
These cells send out electrochemical signals in a 24-hour pattern. This part of
the hypothalamus is connected to other
sections of the brain and many body
systems use its signal to synchronise their activities.
In previous years, biologists had
identified a few individual components
of the clocks used by fruit flies and by a
microbe called neurospora, which
makes bread mould. For years,
Takahashi's group has been
searching for a clock gene in
mice. It administered drugs
that produced random mutations in the animals and then
bred them. The researchers
then screened them for defects
in their biological clock to see
which gene was disrupted.
Among the offspring, the
group found one mouse that
had a defective clock gene. The
mutant mouse had a basic
daily rhythm about an hour longer than normal mice.
When the mouse was bred and its progeny crossbred, the scientists found a
number of animals whose biological
clocks were running four hours longer
than normal. When kept in total darkness, these mice eventually lost all circadian rhythm and their activity was completely disorganised.
It took Takahashi and his team three
years to identify the clock gene and find
out the molecular features of the protein
it specifies. Of special interest to the scientists is the finding that one stretch of the protein produced by the clock gene,
known as domain, resembles that of the
domain seen in the clock proteins of
fruit flies and bread mould, though the
overall protein structures have hardly
any similarity. This lends support to the
theory that the circadian rhythms have a
common basic mechanism in all living
creatures. Steven M Reppert, who studies circadian rhythms at Massachusetts
General Hospital, described the discovery as "the first molecular entry into the
mammalian clock".
The mouse clock protein was found
in abundance not only in the animals'
eyes and in the suprachiasmic nucleus of
the hypothalamus but also in the testis,
ovary, liver, heart, lung and kidney. The
researchers are keen to determine
whether the protein also regulates the
circadian rhythm expression in those
tissues. Report says that revelations of
such kind will help explain such curiously time-related phenomena as the high
incidence of heart attacks in the morning or the increase in asthma at night.
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