Circadian rhythms are biological processes that display endogenous, entrainable oscillations of approximately 24 hours. They are driven by a circadian clock and are found in plants, animals, fungi, and cyanobacteria. In animals, the suprachiasmatic nucleus acts as the master clock, containing genes that govern circadian rhythms. Circadian rhythms allow organisms to anticipate and adapt to daily environmental changes like light and temperature. They persist even in the absence of external cues, showing they are endogenously generated, though environmental cues can entrain or synchronize the rhythms.

1. CIRCADIAN RHYTHM
Abhinaya Alley
Roll no 16cs0055
Bsc zoology homours
Sikkim government science college
West sikkim

2. Definition
• A circadian rhythm is any biological process that displays
an endogenous, entrainable oscillation of about 24 hours.
These 24-hour rhythms are driven by a circadian clock, and
they have been widely observed in plants, animals, fungi,
and cyanobacteria.
• Sleeping at night and being awake during the day is an
example of a light-related circadian rhythm.
• Endogenous: Having an internal cause or origin
• Entrainable oscillation: Rhythmic physiological or behavioral
events which match their period to that of an environmental
oscillation.
• The study of circadian rhythms is called chronobiology.

3. What are biological clocks?
• Biological clocks are an organism’s innate
timing device.
• They’re composed of specific molecules
(proteins) that interact in cells throughout the
body.
• Biological clocks are found in nearly every
tissue and organ.

4. What are Master clocks?
• Master Clock: A pair of cell populations
found in the hypothalamus, known as the
suprachiasmatic nuclei (SCN); these cells
contain the genes that govern circadian
rhythms.
• Biological clocks produce circadian rhythms
and regulate their timing.

5. What causes the behaviour?
• Natural factors within the body produces the
circadian rhythms.
• However, signals from the environment also
affect them which is called zeitgebers
• The main cue influencing circadian rhythms is
daylight. This light can turn on or turn off
genes that control the molecular structure of
biological clocks.

6. • However in the absence of any zeitgeber,
organisms continue to exhibit rhythmicity,
albeit with near 24-h periodicities, indicating
that these rhythms are generated from within
the organism.
• Rhythms exhibited under constant conditions
are termed ‘free-running rhythms’ and the
period of such rhythms as ‘free-running
period.

7. A simplistic model of circadian clocks comprises
three functionally distinct components
1) Input pathways
2) Oscillator
3) Output pathways

8. Is circadian rhythm innate or learned
phenomenon ?

9. • Jürgen Aschoff , a German physician, raised
mice for several generations in constant light
and found that circadian rhythms continued to
persist in the last generation as robustly as
earlier despite the absence of cycling
conditions for several generations thus
indicating that circadian rhythms are an innate
property of the organism.

10. • Further, he also raised chicken in constant
conditions and found that the adults continued
to exhibit rhythmic behaviour, indicating that
no prior exposure to cyclic conditions is
required to develop rhythmicity.

11. Studies on protists like Euglena and Gonyaulax
• circadian rhythms can be modulated or the
rhythm can be abolished by mRNA and protein
synthesis inhibitors.

12. • Ronald J Konopka working with Seymour
Benzer reported the discovery of the first ever
clock gene in Drosophila.
• Through the mutagenesis they disrupted the
functioning of gene responsible for cycle and
found three types of individual:
• With 19 hrs cycle
• With 28 hrs cycle
• With very arrhythmic cycle.

13. Further, mapping revealed that the three
mutations were alleles of the same gene on the
X-chromosome and the gene was named
period (per) since it affected the period of the
rhythm.
Mutations in the same gene rendering the clock
fast or slow or even abolishing the rhythm
further indicated that the per gene is indeed a
component of the central oscillator

14. • The per mRNA and protein levels were found
to exhibit circadian oscillation with their
intracellular concentrations peaking at certain
times of the day and reducing at other times.
• More importantly, the mRNA levels fell when
the respective protein levels began to rise,
hinting at a reciprocal relationship between the
two.
• This implies negative feedback mechanism

15. • Based on emperical observation that per
mRNA level falls as its protein levels peak, it
was inferred that PER protein might act as a
feedback regulator to suppress its own
transcription (possibly by binding to its own
promoter sequence).
• However sequence analysis revels that PER
proteins do not have any known DNA-binding
domain that could mediate binding of PER to
the promoter sequences.

16. • Another breakthrough was made in the year
1994 when a critical clock gene was identified
in 2nd chromosome and is called timeless (tim).
• later reported that TIM physically interact with
PER to form a PER–TIM dimer.
• TIM protein may also influence its own
transcription.

17. • When flashed with a pulse of light, TIM
degraded within 30 min indicating that it is a
photosensitive protein.

18. Cycle of events which occurs in
molecular level in Drosophila .

19. Zeitgebers
• The question of how light affects the molecular clocks?
• In Drosophila, it works like this.
• Light (blue) is absorbed by the
protein cryptochrome (CRY).
• This causes an allosteric change in its conformation
enabling it to bind to TIM and PER.
• This causes TIM and PER to break down (in proteasomes)
ending their inhibition of gene transcription.
– If this happens when PER/TIM levels are rising (late in
the "day"), it sets the clock back.
– If it happens when PER/TIM levels are declining (late
in the "night"), it sets the clock ahead.

21. To summarize
• the molecular components of the core
circadian oscillator in Drosophila involves
transcription factors
• CLOCK and CYCLE that form a CLK–CYC
heterodimer, bind to E-box sequences on the
per and tim genes and induce its transcription
through the day until midnight when the Mrna
levels of both genes peak.

23. • Subsequently, PER and TIM proteins peak by early morning in
the cytoplasm where DBT(DOUBLETIME KINASE) kinase
associates with PER and promotes degradation of PER which
is later stabilized by binding of TIM to PER–DBT complex.
Subsequent phosphorylation by SGG kinase and CK2􀁄
promotes translocation of the PER– DBT–TIM complex to the
nucleus where it displaces CLK–CYC heterodimer from the E-
box thus repressing per and tim transcription and completing
the feedback loop. In addition to this, when lights turn ON in
the morning, TIM in the PER–DBT–TIM complex undergoes
CRY-mediated degradation leaving behind unstable PER–DBT
complex. Due to lack of stability in the absence of TIM, PER
is then targeted for proteasomal degradation by DBT. This set
of events takes approximately 24h to complete and constitutes
one circadian cycle