POSSIBLE FUNCTIONS of the CIRCADIAN CLOCK

IS IT IMPORTANT AT ALL? YES!

POSSIBLE FUNCTIONS DAILY PROGRAMING of PHYSIOLOGY

PHOTOPERIODIC REPRODUCTION

ANIMAL MIGRATION

MCB 186 December 5, 2007

IS THE CIRCADIAN CLOCK IMPORTANT ?

DOES THE CLOCK CONFER SELECTIVE ADVANTAGE?

MAYBE NOT: NULL MUTANTS are VIABLE in ALL STUDIES

TWO KINDS of STUDIES

MEASURE LIFESPAN IN ANIMALS SUBJECTED TO NON-24 hr CYCLES

RESONANCE EXPERIMENTS IN CYANOBACTERIA USING PERIOD MUTANTS

SURVIVIAL CURVES for FLIES in LIGHT/DARK CYCLES with PERIODS of 20, 24 AND 28 HOURS

FIVE HOUR LD PHASE SHIFTS EACH CYCLE

CYANOBACTERIA MUTANTS V.S. WILD TYPE IN DIFFERENT LD CYCLES

C.H. Johnson lab

CYANOBACTERIA MUTANT Tau-28 V.S. WILD TYPE Tau-25

C.H.Johnson lab

Two independent experiments

SOME FUNCTIONS OF THE CIRCADIAN CLOCK

TIMED PHYSIOLOGY: SPECIFIC TIMES OF DAY/NIGHTSynthesis of specific proteins at specific times of day

Insect eclosion acrophase is at time of daily temperature minimum.

The internal bee clock; Visitations timed to time of flower openingsCyanobacteria, photosynthesis by day, nitrogen fixation by night.

PHOTOPERIODIC REPRODUCTION: MEASURE DURATION OF DAY AND NIGHT-Plants: seasonal flowering, spring, summer or fall.-Animal seasonal reproduction; hamster only once per year.

ANIMAL MIGRATION-Celestial navigation for migration (birds, butterflies, arthropods, fish, reptiles); knowledge of time of day required.

TIME of DAY PROGRAMS

• Different activities at different times of day involve different genes and proteins

• In circadian systems, different proteins are synthesized at different times of day

• Cyanobacteria carry out photosynthesis with oxygen production and nitrogen fixation at different times of day. Oxygen inhibits nitrogenase.

BEAN (top) and CANAVALIA CIRCADIAN LEAF MOVEMENTS

DROSOPHILA ENTRAINMENT TO FULL LD CYCLES PITTENDRIGH

ACROPHASE DEPENDS ON PHOTO-FRACTION

TEMPORAL SEPARATION OF CELL BIOCHEMICAL ACTIVITIES IN CYANOBACTERIA (OXYGEN, NITROGENASE ETC) MITSUI ET AL 1986

PATTERNS of CLOCK-CONTROLLED PROTEIN SYNTHESIS in Gony

Markovic et al., 1996J. Biol. Rhythms 11

p21 unknown p32 PCPp33 OEE1p45 GAPDHp55 Rubisco IIp75 Luciferin binding

protein

PHOTOPERIODISM

DISCOVERY: Garner & Allard, 1920

TOBACCO FLOWERING ONLY IN FALL WITH SHORT DAYS OTHER PLANTS SHOWN TO FLOWER WITH LONG DAYS. STILL OTHERS DAY LENGTH NEUTRAL

TERMINOLOGY CORRECTED: Hamner & Bonner, 1938

LENGTH OF THE NIGHT, NOT THE DAY, IS CRITICAL LIGHT INTERRUPTIONS OF NIGHT BLOCK RESPONSE, DARK INTERRUPTIONS OF DAY DO NOT BLOCK

INCORRECT TERMINOLOGY STILL IN USE:

DAY LENGTH AT DIFFERENT LATITUDES & SEASONS

HAMSTER TESTIS WEIGHT IN DIFFERENTFULL PHOTOPERIODS Elliott, 1976

PHOTOPERIODIC INDUCTION OF CYSTS IN GONYAULAX

SOY BEAN (SHORT DAY PLANT) 0.5 hr LIGHT INTERRUPTION of LONG DARK PERIOD WARING, 1954

H. NIGER (LONG-DAY PLANT) 2 hr LIGHT INTERRUPTION OF LONG DARK PERIOD

SOYBEAN (short day) FLOWERING IN DIFFERENT LD CYCLES

MODELS FOR PHOTOPERIODISM

HOUR GLASS: Substance X builds up during dark

Explains night interruption by brief light exposure

Does not explain oscillation of long dark periods.

ENDOGENOUS OSCILLATION

Explains circadian recurrence of susceptibility to brief light exposure during prolonged DD

External Coincidence model:

Night interruption causes delays & advances

EXTERNAL COINCIDENCE: POSTULATED PHOTOPERIODIC EFFECTS ON AN ORGANISM WITH A CIRCADIAN tau OF 24.5 hr

ENTRAINED T of HAMSTER ACTIVITY RHYTHM DEPENDS on PERIOD of SINGLE PULSE T CYCLE and PULSE is

POSITIONED DIFFERENTLY Elliott 1976

Tau for hamster is very close to 24 hBoth T cycles cause phase shifts, + & -

ADVANCES DELAYS

HAMSTER TESTICULAR RESPONSES to T CYCLE PERIOD LENGTH

DROSOPHILA ENTRAINMENT TO FULL LD CYCLES PITTENDRIGH

PHASE ANGLES WITH DIFFERENT TWO PULSE SKELETONS Pittendrigh

BISTABILITY IN HAMSTER ENTRAINMENT SKELETON PHOTOPERIOD 13.5:0.25:10:0.25 hrs

ANIMAL C15 ACTIVE in SHORT NIGHT TESTES MAINTAINED; ANIMAL C16 ACTIVE in LONG NIGHT; TESTES REGRESSED

SKELETON PHOTOPERIOD PHASING GIVES DIFFERENT RESPONSES

ARE HUMANS AFFECTED by PHOTOPERIOD?

It appears so!

• ANNUAL CYCLES

• DAILY ENTRAINMENT PHASE

1824 1947

HUMAN ANNUAL CONCEPTION RHYTHMS

SOCIAL INFLUENCES on the ANNUAL CONCEPTION RHYTHM

SOCIAL INFLUENCES on the ANNUAL CONCEPTION RHYTHM

Effect of Residence Locations on Sleep Acrophase (n=21,600)

Germany

Roenneberg, 2006

DEPENDENCE of TIME of MID-SLEEP on LONGITUDE 8.5O=34min and RELATION to POPULATION DENSITY

Rural and towns less than 300,000 persons

300,000 - 500,000

> 500,000

Roenneberg, 2006

DAYLIGHT SAVING TIME RELATED to SLEEP PHASE and DURATION

CIRCANNUAL RHYTHMS IN SQUIRRELS & GONYAULAX

FUNCTIONS of the CIRCADIAN CLOCK

CELESTIAL NAVIGATION

-Animal migration (birds, butterflies, arthropods, fish, reptiles); knowledge of time of day required.

DIRECTION OF STARLING MIGRATORY ACTIVITYKramer,1950 a) clear sky b)overcast c),d) direction of incident light deflected by mirrors

DIRECTION OF DEPARTURE IN PIGEONS ALTERED AFTER EXPOSURE TO LD CYCLE ALTERED BY 6 hr Schmidt-Koenig,1961

SHIFTING THE DIRECTIONAL RESPONSE OF PIGEONS

DELAYED SLEEP PHASE INSOMMNIA THERAPY

Deficiency in advance phase shifts

Treatment: Impose repeated delaysuntil patient is back in phase.