Biology Reference
In-Depth Information
primitive organisms maintain their homeostasis, let us
begin by asking what evolutionary selection pressures
could have enabled the clock to arise. Among many
possibilities, there is some empirical evidence for the
'escape from light' hypothesis
[8]
. This hypothesis, framed
by Dr Collin Pittendrigh, father of modern chronobiology,
suggests that the selection pressure for clock evolution
was a cellular-coping mechanism against the ionizing
radiation of the sun
[8]
. Certain physiological processes,
such as DNA replication, can be compromised by photo-
damage. Mechanisms that restricted or 'scheduled' such
photosensitive processes to the night could have provided
the earliest push for the evolution of circadian clocks. To
test this hypothesis, Carl Johnson's group tested survival
curves of the unicellular algae Chlamydomonas reinhardtii
after exposure to ultraviolet (UV) radiation at different
times of day
[9]
. These algal cells showed increased
susceptibility to UV radiation at night. An extension of this
hypothesis is the temporal compartmentalization of some-
what antagonistic processes. For example, in unicellular
cyanobacteria, biochemically incompatible reactions such
as oxidation/reduction, photosynthesis/nitrogen fixation,
etc., are scheduled for different times of the day, an elegant
solution
[8,10]
.
Next let us ask, how did the clock machinery evolve to
its current state? There are two models to describe the
evolution of clock mechanisms:
(1)
the classic model
Additionally, finer differences are observed, such as non-
overlapping clock gene expression patterns between the
silk moth, Drosophila and mice
[16
19]
. Thus the
convergent model proposes that evolutionarily distinct
pacemakers converged to a feedback activation
e
repression
loop mechanism, presumably because of their robustness in
generating 24-hour rhythmic oscillations. Although strong
empirical evidence is still lacking, as it often is for evolu-
tionary arguments, clocks could have evolved by a process
that included both the above-mentioned models.
Why do we and most other organisms on Earth still have
a clock? This is particularly interesting for nocturnal
rodents, who are largely shielded from the radiation of the
sun. For example, the blind subterranean mole rat, Spalax
ehrenbergi, lives in total darkness but still has a circadian
clock
[20]
. A salient feature of the circadian pacemaker is
its ability to maintain robust oscillation with conserved
amplitude, period length and phase even when faced with
acute environmental perturbations. Our circadian pace-
makers are resistant to acute environmental perturbations
such as diurnal changes in temperature (morning vs.
afternoon), light (cloudy vs. clear sky), humidity etc.,
allowing us to keep track of time. However, clocks are also
adaptable to prolonged perturbations such as seasonal
changes in day length or temperature
[8,21,22]
. Thus the
most fundamental advantage of an internal clock is to
synchronize one's behavior/physiology to the state of the
prevailing environment.
Some of the adaptive advantages of biological clocks
have now been identified and related to various facets of
survival in the wild. Examples include avoiding predators
(animals with lesioned central clock do not survive as well
as non-lesioned animals in the wild;
[23,24]
), preventing
desiccation (an example is the timed eclosion rhythms of
the fruitfly larvae to the morning, when humidity is rela-
tively high;
[25]
), finding mates (temporal separation by
speciation;
[26]
), synchronizing feeding with food avail-
ability, and tuning metabolic pathways to allow seasonal
features such as hibernation.
In summary, it is important to appreciate that evolution
favors mechanisms that work
e
e
complex clocks evolved by refinements of a primitive
clock, and
(2)
the convergent model
repeated but inde-
pendent selection pressure led to the generation of clocks
across the entire biosphere
[8,11,12]
. The classic model
refers to the prevalence of the PAS domain (named after the
three founding members of the PAS domain superfamily,
Drosophila PER, mammalian ARNT and Drosophila SIM)
in clock-related proteins throughout the evolutionary tree
of life
[13]
. PAS domains were originally identified as
protein
e
protein interaction domains, but were subse-
quently found to also bind small ligands (e.g., in the aryl
hydrocarbon receptor
[14]
). However, reports suggest that
PAS domains have evolved from ancient environment-
sensing proteins. Based on homology, PAS domains could
have evolved from LOV (light, oxygen, voltage sensing;
[13,15]
) and/or bacterial blue-light receptor, photoactive
yellow protein (PYP; 13) domains. Incorporation of these
environmental sensing domains in an oscillatory feedback
loop with a 24-hour period could have initiated clock
evolution. Evolutionary fitness provided by the circadian
system ensured its selection over time, albeit with growing
complexity.
In contrast, the convergent model draws attention to the
differences in the oscillators. The most compelling argu-
ment here has been the complete lack of homology of clock
genes in cyanobacteria, plants, and animals, suggesting that
circadian rhythms have evolved at least three times
[12]
.
e
anticipating and reacting to
changes
in the environment such as light, temperature and
humidity, is an integral part of this survival strategy. For the
rest of this chapter we will focus on our current under-
standing of the adaptive advantages of the mammalian
biological clock, with an emphasis on its role in behavior,
physiology, and molecular homeostasis.
e
ROLE OF THE CLOCK IN NEUROLOGICAL
FUNCTIONS
Before we begin our discussion on neurophysiological
functions of the clock, let us review the organization of the
