The sun; SOHO's EIT (Extreme-Ultraviolet Imaging Telescope)

Earth-moon system from Galileo-1990

(from NASA photo gallery)

The astronomer Jean Jacques d’Ortous deMairan is usually credited with discovering “circadian rhythms”in heliotrope plants in 1729

Properties of Circadian Rhythms

• Name is derived from “circa” (approximately) and “diem” (day)

• When organisms are placed in constant conditions of DD or dim LL, they express a circadian rhythm with a period () of slightly less or slightly more than 24 hrs

• These rhythms must be synchronized or “entrained” to local time so that the phase ( of the internal rhythm corresponds to the of the outside world.

Prokaryotes suchas cyanobacteria (in this case Synechococcus sp.) expresscircadian rhythms in gene expression with a of about 24 hrs

(from Golden et al. 1999)

24 hours ofgrowth

one circadian cyclePoint ofinoculation

side

top

Diagram of a race tubeFungi, such as the orange bread mold, Neurospora crassa, expressa wide variety of circadian patterns. In this case, patterns ofconidiation, or asexual spore formation, occur every 19-20 hrs.

(from Bell-Pedersen, 1999)

Complex, multicellular animalsexpress a wide variety ofcircadian rhythms. In this case, the activity/sleep and bodytemperature patterns of a single human subject is expressedin actogram format. The average is 24.1-25 hrs

(from Aschoff, 1981)

What are Biological Clocks?• Simply put, “biological clocks” are mechanisms

by which organisms can tell time. The enable living things to predict internal and external events.– Internal oscillator– Zeitgeber or synchronizer– Output pathways

• These clocks predict periods of varying magnitude– Annual (circannual)– Daily (circadian)

Zeitgeber

Input Pathway

CircadianClock

OutputPathways Outputs

General Model of Circadian Clocks

The Hypothalamic Suprachiasmatic Nucleus (SCN) is the

Master Pacemaker for Nocturnal Rodents and Probably

Many, If Not All, Mammals

(from Bittman, 1984)

Fig. 1a

01

234

567

89

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Time in Culture

2-D

G U

pta

ke

SCN/3T3-WELLS

SCN/3T3-INSERTS

Fig. 1b

0

0.5

1

1.5

2

2.5

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Time in Culture

2-D

G U

pta

ke

3T3/3T3-WELLS3T3/3T3-Inserts

SCN 2.2 Cells Induce Circadian Rhythms in NIH3T3 Cells

(from Allen, Rappe, Cassone and Eannest, 2000)

SCNX

SCN2.2

SCNX

NIH3T3

SCN2.2 Cells Restore Circadian Rhythms NIH3T3 Cells Do Not

(from Earnest, Liang, Ratliff and Cassone, 1999)

Recent advances in molecular genetics has identified specific genes that are important for circadian rhythms in many different types oforganisms that are expressed rhythmically in clock-associated tissues. This is the expression pattern of mouse period genes in the SCN.

(from Maywood et al. 2000)

               

 

“Common” Elements of Circadian Clocks

Positive Elements Negative

Elements

Clock Genes

Output (CCGs)

Rhythmic MetabolismAnd Behavior

Positive Elements in circadian loops:kaiA in Synechococcuswc1 and wc2 in NeurosporaClk, cyc, clock and bmal1 in animals

Negative Elements in circadian loops:kaiC in Synechococcusfrq in NeurosporaPer, cry and tim in animals

In Mammals, At Least, Pineal Rhythmicity Derives PrimarilyFrom Rhythmic SCN Input via the Sympathetic Nervous System

(from Bittman 1984)

(from Richter, 1967)

Pinealectomy has no effect of rodent locomotor rhythms in DD

(from Redman, Ng, and Armstrong, 1983)

But Daily AdministrationOf the Pineal HormoneMelatonin Entrains RatCircadian Rhythms.

This Effect is Dose- and Phase-Dependent with anED50 of 1-5 g/kg (Cassone et al. 1986; Warren et al. 1993), Independent of the PinealGland (Warren et al. 1993)and Does Not RequireInjections (ie. Infusionsof Melatonin Work; Kirsch et al.1993)

Circadian Rhythms in the Classroom

• Visit Website for the NSF Center for Biological Timing to learn more about clocks– http://cbt4pc.bio.virginia.edu/tutorial

• Also, there are specific classroom and home activities listed in that site at– http://cbt4pc.bio.virginia.edu/tutorial/CLASSACT.html

Visit the Biological Clocks ProgramAt Texas A&M at http://www.bio.tamu.edu/clocks/

A copy of this presentation can be found at the following websitehttp://www.bio.tamu.edu/facmenu/faculty/cassone.htm