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Transcript
Biological clocks
• Clock periods
– Circannual
– Circalunidian
– Circadian
• Clock mechanisms
– Entrainment
– Neural location
– Genetic basis
Hibernation follows annual rhythm in
golden-mantled ground squirrels
Five animals were isolated at birth and kept in darkness at 3oC
Testes growth and
feather molt in
stonechats follows
annual cycles
Quick Time™a nd a TIFF ( Uncomp res sed) deco mpre ssor are n eede d to s ee this picture .
Nestlings were removed from Kenya
and reared in Germany with constant
temperature and photoperiod and yet
retain annual molt and testes cycles.
Notice that the clock period drifted.
Horseshoe crabs mate on full moon
why?
Lunar position affects the tides
Spring tide
Neap tide
Sun and moon
align, tidal
excursion is
greatest
Sun and moon
are perpendicular,
tidal excursion is
least
Neotropical bats exhibit lunar phobia
Kangaroo rat
feeding shows
lunar cycles
K-rat activity at a
feeder is confined to
dark periods
Quic kTime™ and a TIFF (Uncompres sed) dec ompres sor are needed to see this picture.
occurred during period
of seed shortages
Isopod activity follows daily tidal flow
Isopods are usually covered with water at high tide. They retain
this activity even when kept in the lab with no tidal fluctuation.
Entrainment by environmental cycles
• Temperature compensation
– Clock cycles do not change with temperature
• Environmental cues set cycle period
– Species specific
• Types of cues (zeitgebers)
– Photoperiod
– Light pulse
– Food availability
Cricket calling entrains to dark
Constant light
for 12 days
12 h light/dark
for 12 days
Mouse activity entrains to light
12h light:12h dark
24 h dark
10 min light
10 mins of light per day are sufficient to reset the clock
Mole-rats lack daily cycles
Clock mechanisms
• Location of the clock
– Suprachiasmatic nucleus of the hypothalamus
– Pineal gland
• Clock genes
– Period
– Timeless
– Tau (doubletime)
Mammal and
bird clocks
reside in the
suprachiasmatic
nuclei (SCN),
which is in the
hypothalamus
Period
In hamsters,
SCN lesion disrupts
clock while SCN
transplant restores
clock
Isolated rat
SCN cells
exhibit clock
activity
Isolated caudate (upper
brainstem) cells do not
cycle, but isolated SCN
cells do cycle
Isolated neurons from rat SCN
exhibit circadian rhythym
Neural firing is stopped with application of tetrodotoxin (TTX),
which blocks sodium channels, but clock kept ticking!
Pineal glands respond to light cycles
Melatonin release from chicken pineal glands cultured in vitro
Light cycles
No light cycles
Distribution of
circadian clocks in
tissues and taxa
Mammalian
clock
pathways
period alleles exhibit altered circadian rhythyms
in Drosophila melanogaster
Genetic basis of the clock in flies
http://www.nimh.nih.gov/publicat/bioclock.cfm
• NOON: per and tim genes are turned
on by CLOCK-CYCLE complex,
which binds to promoter
• SUNSET: PER and TIM transcription
occurs
• NIGHT: PER and TIM proteins build
up inside the cell, and as a complex
can enter nucleus
• dbt codes for an enzyme that adds a
phosphate to PER, which causes it to
be destroyed & adds time delay
• DAWN: Cryptochromes absorb blue
light and activate cry gene expression.
TIM protein is degraded by CRY
protein.
• PER is released from PER-TIM
complex and broken down, so
CLOCK-CYCLE can activate per and
tim
Genetic basis of the clock in mammals
• per codes for a protein
(PER) that gradually builds
up over time
• tau codes for an enzyme
that breaks down PER
• tim codes for a protein
(TIM) that binds with PER
to cross the membrane and
suppress transcription of
PER
• Photoreceptor not yet
known
• Cycle repeats every 24 h
Clock summary
• per/tim/tau(dbt) genes control pacemaker
• Pacemaker occurs in SCN in vertebrates, but is
distributed in brain cells in some insects
• SCN signals pineal to release melatonin.
Melatonin causes entrainment
• Short pulses of light entrain SCN and pineal cells
– Photoreceptors occur in the pineal and eyes of birds
– Photoreceptors occur in retina of mammals
• Drosophila, honey bees, hamsters and humans
share same genes - likely common ancestor was a
flatworm that lived about 600 MYA
Clock neurons in fly brains
http://www.bio.brandeis.edu/faculty/hall.html
Hall, J.C. 2003. Genetics and molecular biology of rhythms in Drosophila and other insects. Adv.
Genet. 48: 1-286