Circadian oscillation of a mammalian homologue of the Drosophila period gene

Abstract

Many biochemical, physiological and behavioural processes in organisms ranging from microorganisms to vertebrates exhibit circadian rhythms¹. In Drosophila, the gene period (per) is required for the circadian rhythms of locomotor activity and eclosion behaviour². Oscillation in the levels of per mRNA and Period (dPer) protein in the fly brain is thought to be responsible for the rhythmicity³,⁴. However, no per homologues in animals other than insects have been identified. Here we identify the human and mouse genes (hPER and mPer, respectively) encoding PAS-domain (PAS, a dimerization domain present in Per, Amt and Sim)-containing polypeptides that are highly homologous to dPer. Besides this structural resemblance, mPer shows autonomous circadian oscillation in its expression in the suprachiasmatic nucleus, which is the primary circadian pacemaker in the mammalian brain⁵,⁶. Clock, a mammalian clock gene encoding a PAS-containing polypeptide⁷,⁸, has now been cloned: it is likely that the Per homologues dimerize with other molecule(s) such as Clock through PAS–PAS interaction in the circadian clock system.