CIRCADIAN CLOCK LOCUS FREQUENCY - PROTEIN ENCODED BY A SINGLE OPEN READING FRAME DEFINES PERIOD LENGTH AND TEMPERATURE COMPENSATION

The frequency (frq) locus encodes a key component, a state variable, i n a cellular oscillator generating circadian rhythmicity. Two transcri pts have been mapped to this region, and data presented here are consi stent with the existence of a third transcript. Analysis of cDNA clone s and clock mutants from this region focuses attention on one transcri pt encoding a protein. FRQ, which is a central clock component: (i) mu tations in all of the semidominant frq alleles are the result of singl e amino acid substitutions and map to the open reading frame (ORF) enc oding FRQ; (ii) deletion of this ORF, or a frameshift mutation within it, results in a strain with a recessive clock phenotype characterized by the loss of rhythm stability and compensation. Single amino acid s ubstitutions within, or disruption of, this single ORF are thus suffic ient to drive major alterations in both period length and temperature compensation, two canonical characteristics of circadian systems. The 989-amino acid FRQ protein specifies the circadian function of frq in the assembly of the Neurospora biological dock.