Abstract:
Circadian clocks are endogenous time keeping systems whose period is largely protected
against changes in ambient conditions. Nevertheless, they can be fine-tuned by
environmental time cues (Zeitgebers) in a way that the period becomes indistinguishably
close to 24 hr, and acquires a unique and reproducible phase-relationship with the
environmental cycles (Daan and Aschoff, 2001). These clocks drive a variety of
behavioural and physiological rhythms in a wide range of organisms from bacteria to
humans, and help organisms in anticipating daily and seasonal events in their
environment (Dunlap et al., 2004; Allada and Chung et al., 2010). Circadian clocks are
believed to be of great adaptive value to organisms living under periodic as well as
constant conditions as they enhance their fitness by coordinating various behavioural and
physiological processes to external environmental and internal metabolic cycles (Ouyang
et al., 1998; Sharma, 2003a). The earliest step to characterize the rhythm
generating/regulating mechanisms at the gene level was taken in 1971 by Konopka and
Benzer, when they found that three alleles of a newly discovered gene period (per) - per
L
(long period of ~ 29hr), per
S
(short period of ~ 19hr) and per
0
(arrhythmic phenotype)
have impact on the activity/rest and adult emergence rhythms (Konopka and Benzer,
1971). Following the identification of per gene, other clock genes such as timeless (tim),
clock (clk), cycle (cyc), and Cryptochrome (cry) in Drosophila; frequency (frq) and white
collar (wc-1,wc-2) in Neurospora; and KaiA, KaiBC in cyanobacteria; Clock (Clk),
Period1-3 (Per1-3), Bmal1, and Cry1-2 in mammals were identified (Shearman 2000;
9
Johnson 2001; Cheng et al 2001; Allada and Chung, 2010; Dunlap et al., 2004).