Circadian rhythms in Neurospora crassa: interactions between clock mutations.

Mutations at four loci in Neurospora crassa that alter the period of the circadian rhythm have been used to construct a series of double mutant strains in order to detect interactions between these mutations. Strains carrying mutations at three of these loci have altered periods on minimal media: prd-1, several alleles at the olir (oligomycin resistance) locus and four alleles at the frq locus. A mutation at the fourth locus, cel, which results in a defect in fatty acid synthesis, also leads to lengthening of the period when the medium is supplemented with linoleic acid (18:2). The cel mutation was crossed into strains carrying the frq, prd-1 and olir mutations, and the periods of the double mutant strains with and without 18:2 supplementation were determined. In addition, data from the literature for other combinations of loci and/or chemical effects on the period have been reanalyzed.--It was found that both prd-1 and olir are epistatic to the effects of 18:2 on cel; in the series of cel frq double mutant strains, the period-lengthening effect of 18:2 is inversely proportional to the period of the frq parent, indicating an interaction between frq and cel; period effects reported in the literature can be described as changes by a fixed ratio or percentage of the period rather than by a fixed number of hours, and the data, therefore, can support a multiplicative as well as an additive model.--Several biochemical interpretations of these interactions are discussed, based on simple chemical kinetics, enzyme inhibition kinetics and the control of flux through metabolic pathways.