The genetic basis of the circadian clock: identification of frq and FRQ as clock components in Neurospora.
Genetic approaches to the identification of clock components have succeeded in two model systems, Neurospora and Drosophila. In each organism, genes identified through screens for clock-affecting mutations (frq in Neurospora, per in Drosophila) have subsequently been shown to have characteristics of central clock components: (1) mutations in each gene can affect period length and temperature compensation, two canonical characteristics of circadian systems; (2) each gene regulates the timing of its own transcription in a circadian manner; and (3) in the case of frq, constitutively elevated expression will set the phase of the clock on release into normal conditions. Despite clear genetic and molecular similarities, however, the two genes are neither molecular nor temporal homologues. The timing of peak expression is distinct in the two genes, frq expression peaking after dawn and per expression peaking near midnight. Also, although expression of per from a constitutive promoter can rescue rhythmicity in a fly lacking the gene, constitutive expression of frq will not rescue rhythmicity in Neurospora frq-null strains, and in fact causes arrhythmicity when expressed in a wild-type strain. These data suggest that frq is and/or encodes a state variable of the circadian oscillator. Recent molecular genetic analyses of frq have shed light on the origin of temperature compensation and strongly suggest that this property is built into the oscillatory feedback loop rather than appended to it. It seems plausible that clocks are adjusted and reset through adjustments in central clock components such as frq, and, by extension, per.
Dunlap
J C
JC
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755-3844, USA.
Loros
J J
JJ
Aronson
B D
BD
Merrow
M
M
Crosthwaite
S
S
Bell-Pedersen
D
D
Johnson
K
K
Lindgren
K
K
Garceau
N Y
NY
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009491:Neurospora / Q000502:physiology*
D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; C082454:Frq protein, Drosophila; D009419:Nerve Tissue Proteins