Genetics and molecular biology of rhythms

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Abstract
Mutations that disrupt biological rhythms have existed in microbial and metazoan eukaryotes for some time. They have recently begun to be studied with increasing intensity, both in terms of phenotypic effects of the relevant genetic variants, and with regard to molecular isolation and analysis of the genes defined by two of the ‘clock mutations’. These genetic loci, called period (per) in Drosophila and frequency (frq) in Neurospora, influence not only the basic characteristics of circadian rhythmicity, but also temperature compensation of such daily cycle durations, ‘re‐setting’ of the rhythms' phases, and (for the per mutants) behavioral oscillations associated with much shorter than circadian periodicities. Molecular cloning of Drosophila's per gene, accompanied crucially by the locus's identification in germ‐line transformants, has led to information on its expression ‐ temporally, spatially, and in regard to heterogeneity of mRNA types. Nucleotide‐sequencing analyses of genomic DNA (and/or cDNA) from normal and mutated per alleles have (1) led to the suggestion that this clock gene encodes a family of proteoglycans (which was further indicated by application of antibody reagents obtained by manipulation of one of the gene's exons); and (2) shown that the three types of per mutations ‐ which shorten or lengthen rhythm periodicities or appear to eliminate them ‐ are associated with interesting amino‐acid substitutions or a stop codon, respectively. Analogous molecular findings are awaited from Neurospora, whose frq gene has very recently been cloned and definitively identified, in part via transformation experiments.