Highly conserved Drosophila ananassae timeless gene functions as a clock component in Drosophila melanogaster (original) (raw)
Related papers
Molecular and Cellular Biology, 1998
The Clock gene plays an essential role in the manifestation of circadian rhythms (≅24 h) in mice and is a member of the basic helix-loop-helix (bHLH) PER-ARNT-SIM (PAS) superfamily of transcription factors. Here we report the characterization of a novel Drosophila bHLH-PAS protein that is highly homologous to mammalian CLOCK. (Similar findings were recently described by Allada et al. Cell 93:791–804, 1998, and Darlington et al., Science 280:1599–1603, 1998.) Transcripts from this putative Clock ortholog (designated dClock ) undergo daily rhythms in abundance that are antiphase to the cycling observed for the RNA products from the Drosophila melanogaster circadian clock genes period ( per ) and timeless ( tim ). Furthermore, dClock RNA cycling is abolished and the levels are at trough values in the absence of either PER or TIM, suggesting that these two proteins can function as transcriptional activators, a possibility which is in stark contrast to their previously characterized role...
Genetics, 2000
In genetic screens for Drosophila mutations affecting circadian locomotion rhythms, we have isolated six new alleles of the timeless (tim) gene. Two of these mutations cause short-period rhythms of 21–22 hr in constant darkness, and four result in long-period cycles of 26–28 hr. All alleles are semidominant. Studies of the genetic interactions of some of the tim alleles with period-altering period (per) mutations indicate that these interactions are close to multiplicative; a given allele changes the period length of the genetic background by a fixed percentage, rather than by a fixed number of hours. The timL1 allele was studied in molecular detail. The long behavioral period of timL1 is reflected in a lengthened molecular oscillation of per and tim RNA and protein levels. The lengthened period is partly caused by delayed nuclear translocation of TIML1 protein, shown directly by immunocytochemistry and indirectly by an analysis of the phase response curve of timL1 flies.
A new gene encoding a putative transcription factor regulated by the Drosophila circadian clock
The EMBO Journal, 1997
The recently isolated tim gene (Gekakis et al., 1995; Circadian rhythms of locomotor activity and eclosion Myers et al., 1995), is a major per partner in the circadian in Drosophila depend upon the reciprocal autoregulafeedback loop mechanism (Reppert and Sauman, 1995; tion of the period (per) and timeless (tim) genes. As Rosbash, 1995). tim mRNA abundance cycles with the part of this regulatory loop, per and tim mRNA levels same phase as per mRNA in fly heads, and tim as well oscillate in a circadian fashion. Other cycling tranas per mRNA oscillations depend upon both PER and tim scripts may participate in this central pacemaker protein (TIM) (Hardin et al., 1990; Sehgal et al., 1995). mechanism or represent outputs of the clock. In this Like PER levels, TIM levels fluctuate with a 6 h lag paper, we report the isolation of Crg-1, a new circabehind tim transcript cycling (Hunter-Ensor et al., 1996; dianly regulated gene. Like per and tim transcript
The Novel Drosophila timblind Mutation Affects Behavioral Rhythms but Not Periodic Eclosion
Genetics, 2005
Circadian clock function depends on the tightly regulated exclusion or presence of clock proteins within the nucleus. A newly induced long-period timeless mutant, tim blind , encodes a constitutively hypophosphorylated TIM protein. The mutant protein is not properly degraded by light, and tim blind flies show abnormal behavioral responses to light pulses. This is probably caused by impaired nuclear accumulation of TIM BLIND protein, which we observed in brain pacemaker neurons and photoreceptor cells of the compound eye. tim blind encodes two closely spaced amino acid changes compared to the wild-type TIM protein; one of them is within a putative nuclear export signal of TIM. Under constant conditions, tim blind flies exhibit 26hr free-running locomotor rhythms, which are not correlated with a period lengthening of eclosion rhythms and period-luciferase reporter-gene oscillations. Therefore it seems possible that TIM-in addition to its well-established role as core clock factor-functions as a clock output factor, involved in determining the period length of adult locomotor rhythms.
Molecular coevolution within a Drosophila clock gene
Proceedings of the National Academy of Sciences, 1998
The period ( per ) gene in Drosophila melanogaster provides an integral component of biological rhythmicity and encodes a protein that includes a repetitive threonine-glycine (Thr-Gly) tract. Similar repeats are found in the frq and wc2 clock genes of Neurospora crassa and in the mammalian per homologues, but their circadian functions are unknown. In Drosophilids, the length of the Thr-Gly repeat varies widely between species, and sequence comparisons have suggested that the repeat length coevolves with the immediately flanking amino acids. A functional test of the coevolution hypothesis was performed by generating several hybrid per transgenes between Drosophila pseudoobscura and D. melanogaster, whose repetitive regions differ in length by about 150 amino acids. The positions of the chimeric junctions were slightly altered in each transgene. Transformants carrying per constructs in which the repeat of one species was juxtaposed next to the flanking region of the other were almost ...
Molecular rhythms that regulate rhythm genes in Drosophila
Almost all living organisms display rhythms in their activities coinciding with the day-night cycles. Our current understanding of the molecular regulation of circadian rhythmicity in Drosophila comes from studies integrating genetics and molecular biology, and Drosophila is perhaps one of the best understood models in the field of circadian rhythm research. Following the initial discovery of the per (period) gene some decades ago, several other genes, viz. timeless, dclock, cycle, and double-time, that function in the generation of circadian rhythms, have been identified during the past three years: Molecular genetic studies have provided exciting insights into the regulation of the body clocks. Heterodimeric complexes of positive elements (dCLOCK and CYCLE) and their interactions with feedback loops and negative elements of per and tim genes and their products have been identified and these are providing clues to the general layout of the molecular loops that generate circadian rhythms. The lark gene, which encodes an RNA-binding protein, might function as a regulatory element in the circadian clock output pathway controlling pupal eclosion rhythms. However, a clear picture of the output pathways or downstream processes through which the clock regulates the circadian rhythmic events is yet to be understood.