Our goal... is to define the biochemical machinery that
underlies the mysterious yet ubiquitous process of circadian rhythmicity. Our
entree into the process was the period (per) gene of Drosophila melanogaster.
Michael Rosbash, "Molecular Genetics of RNA Processing and Behavior,"
HHMI Research in Progress, 1999.
This research provides direct evidence that clocks in
mammals may be built with the same principles as those seen in fruit flies and
Joseph Takahashi, referring to research on the mammalian Clock
gene, NSF news release, 1997.
It is now three decades since the first known biological clock gene, per, was
identified. Since that time, additional clock genes have been discovered in
Drosophila, and clock genes have been discovered in organisms ranging from bread
mold to mammals. The biochemical mechanisms that are responsible for the
biological clockworks are beginning to be understood in detail. For most
organisms studied so far, the clock mechanism seems to depend on a biochemical
feedback loop that has a positive and a negative arm.
The first circadian gene to be cloned in mammals a gene known as Clock was
cloned and sequenced in 1997. That same year, human and mouse versions of the
per gene were identified.
Drosophila melanogaster Genome Map, as Published in Science, March 24, 2000.
The per gene, whose location on the X chromosome is shown, is one of an estimated
13,600 genes (99% of which have been sequenced).
Click to watch the animation
The Chemical Tick Tock of a Drosophila Clock.
This animation sequence illustrates the major steps in the molecular feedback
loop producing clock function in a Drosophila cell. It shows how four proteins
CLK, CYC, PER, and TIM produce the core chemical oscillation that runs the
biological clock. The proteins and the genes that produce them work in teams of
two. The negative and positive feedback loops shown here rely on transcription,
translation, and the binding of PER and TIM proteins and are very similar in
A Renowned Hamster The Tau Mutant.
In 1988, researchers discovered a Syrian hamster with a mutation called tau
that caused its circadian clock to run fast. It was first circadian mutation to
be identified in a mammal. Researchers have since cloned the tau gene and
identified the enzyme, called casein kinase I epsilon, for which it encodes.
Making Light of Circadian Rhythms The Role of Photopigment Molecules.
Cryptochromes in animals and phytochromes in plants are light-sensitive proteins
that can transmit a signal containing information about light. Because
cryptochrome has proven difficult to crystallize, its molecular structure is not
fully known. This image represents a hypothetical structural model of Drosophila
melanogaster cryptochrome. It was generated by comparing its amino acid sequence
(purple, gray, and green structures) and two different chromophores (yellow, red,
and blue structures) to that of a similar light sensitive protein found in
bacteria (DNA photolylase) whose structure is known. Chromophores are the
reactive centers of cryptochromes.
Mouse Matters Per Turns Up in Mice.
Per, the gene first found in Drosophila, is also found in mice and other mammals.
In mice, the Per1 gene is located on chromosome #11 (shown here in yellow).
Usually, researchers are able to track a gene that has been found in one organism
to other organisms by searching for corresponding sequences. That method did not
work for mammalian Per, because the sequences did not directly correspond to
those of Drosophila per.To date, three variants of mammalian Per have been