A second timeless gene in Drosophila shares greater sequence similarity with mammalian tim

The clock genes period (per) and timeless (tim) of Drosophila melanogaster encode cardinal components of the fly’s endogenous clock [1,2]. Their mRNAs and proteins oscillate in abundance with a lag of about 4–6 hours between their respective peaks in numerous cells throughout the Drosophila body and brain. Per and Tim proteins participate in a negative autoregulatory feedback loop, providing a relentless circadian molecular oscillation [1,2]. A mammalian tim homologue has also been proposed [3,4] but appears to play a minor role in the mammalian clock [5]. In addition, and in contrast to Drosophila, in which a null mutation is viable, a knockout of murine tim (mmTim) is lethal, revealing an essential requirement for mmTim in development [6]. These discrepancies between the tim genes of the two taxa prompted us to investigate the possible existence of paralogues of the tim gene. Southern hybridisation of Musca domestica genomic DNA with a D. melanogaster tim probe indicated the possible presence of two tim related sequences (data not shown). Furthermore, partial sequence data from a Bombyx mori tim-like cDNA clone isolated in our laboratories revealed an unexpectedly higher R512 Current Biology Vol 10 No 14