Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock

@article{Baylies1987ChangesIA,
  title={Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock},
  author={Mary K. Baylies and Thaddeus A. Bargiello and F Rob Jackson and Michael W. Young},
  journal={Nature},
  year={1987},
  volume={326},
  pages={390-392}
}
The period (per) locus, which controls biological rhythms in Drosophila, was originally defined by three chemically induced mutations1. Flies carrying the per° mutation were arrhythmic, whereas pers and perl mutants had circadian behavioural rhythms with 19-hour and 29-hour periodicities, respectively1. Wild-type flies have 24-hour rhythms. Here we compare the per locus DNA sequences of the three mutants with the parental wild-type. The pers and perl mutations lead to amino-acid substitutions… 
The Drosophila genes timeless and period collaborate to promote cycles of gene expression composing a circadian pacemaker.
  • M. W. Young
  • Biology, Medicine
    Progress in brain research
  • 1996
TLDR
The results suggest that the changes in the abundance or activities of PER proteins may be a part of the normal mechanism by which circadian behavioral rhythms are endogenously generated and reset by environmental stimuli.
Cis-Combination of the Classic perS and perL Mutations Results in Arrhythmic Drosophila with Ectopic Accumulation of Hyperphosphorylated PERIOD Protein
TLDR
The results indicate that the semidominant effects of period-altering alleles observed in trans are not necessarily preserved in the cis-configuration and that novel phenotypes can emerge.
The Drosophila double-timeS Mutation Delays the Nuclear Accumulation of period Protein and Affects the Feedback Regulation of period mRNA
TLDR
Results suggest that dbt can regulate the feedback of per protein on its mRNA by delaying the time at which it is translocated to nuclei and altering the level of nuclear PER during the declining phase of the cycle.
The tim SL Mutant Affects a Restricted Portion of the Drosophila melanogaster Circadian Cycle
TLDR
It is proposed that TIM and PER phosphorylation are normally rate determining during the mid-late night region of the circadian cycle, consistent with the notion that this portion of the cycle is governed by unique rate-limiting steps.
The molecular control of circadian behavioral rhythms and their entrainment in Drosophila.
  • M. W. Young
  • Medicine, Biology
    Annual review of biochemistry
  • 1998
TLDR
The recent discovery of PER homologues in mice and humans suggests that a related mechanism controls mammalian circadian behavioral rhythms.
The period gene encodes a predominantly nuclear protein in adult Drosophila
TLDR
The results of an immunoelectron microscopic analysis of wild-type flies and per-beta- galactosidase (beta-gal) fusion gene transgenics using a polyclonal anti-PER antibody or an anti- beta-gal antibody suggest that PER acts in that subcellular compartment to affect circadian rhythms.
The clock gene period in the housefly, Musca domestica : a molecular analysis
TLDR
A comparative study suggests that the current model based on the negative feedback loop may be inadequate to explain the molecular mechanism underlying the circadian clock.
The analysis of new short-period circadian rhythm mutants suggests features of D. melanogaster period gene function.
TLDR
The findings suggest that short-period per mutants are not unusual gain-of-function mutants but rather more traditional loss- of- function mutants that are unable to influence the circadian pacemaker in a proper manner and may engage in important intermolecular interactions.
Genetics and molecular biology of rhythms
  • J. C. Hall, M. Rosbash
  • Biology, Medicine
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1987
TLDR
Nucleotide‐sequencing analyses of genomic DNA (and/or cDNA) from normal and mutated per alleles have led to the suggestion that this clock gene encodes a family of proteoglycans, and shown that the three types of per mutations are associated with interesting amino‐acid substitutions or a stop codon, respectively.
New short period mutations of the Drosophila clock gene per
TLDR
A wide variety of missense mutations, affecting a region of the per protein consisting of approximately 20 aa, predominantly generate short period phenotypes, which suggests that short period Phenotypes may result from loss or depression of function in this domain of theper protein.
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References

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Restoration of circadian behavioural rhythms by gene transfer in Drosophila
TLDR
It is reported that when a 7.1-kb fragment from a per+ fly, including the sequences encoding the 4.5-kb transcript, is introduced into the genome of a per0 (arrhythmic) fly by P element-mediated transformation, circadian rhythmicity of behaviour such as eclosion and locomotor activity is restored.
Product of per locus of Drosophila shares homology with proteoglycans
TLDR
A fragment of DNA of ∼7 kilobases (kb) encoding a 4.5-kb poly(A)+ RNA restores rhyth-micity when transduced into Drosophila carrying mutations5,6 or chromosomal deletions5 of the per locus and the sequence of this biologically active segment of DNA is reported.
Circadian rhythms in Drosophila melanogaster: analysis of period as a function of gene dosage at the per (period) locus.
TLDR
Three possible roles for the per gene product in circadian rhythmicity are discussed, including a role in synchronizing rhythm-producing cells and an explanation for the partial dominance of pers over per+ and the dominance of per+ over per1.
A biological clock in Drosophila.
TLDR
It is suggested that the periodicity of circadian rhythms in Drosophila is determined by the level of expression of a per locus protein encoded by the 4.5-kb transcript.
Molecular analysis of the period locus in Drosophila melanogaster and identification of a transcript involved in biological rhythms
TLDR
Evidence is discussed, from previously reported genetic and phenotypic analysis of per's function, suggesting that this region may be complex and that several gene products from the per region, including this 0.9 kb transcript, may be involved in the different aspects of normal rhythmicity influenced by this clock gene.
An unusual coding sequence from a Drosophila clock gene is conserved in vertebrates
TLDR
The results of a search for sequences homologous to the per locus DNA in the genomic DNA of several species of vertebrates show an unusual, tandemly repeated sequence forming a portion of the 4.5-kb per transcript is homologously to DNA in chicken, mouse and man.
Germ-line transformation involving DNA from the period locus in Drosophila melanogaster: overlapping genomic fragments that restore circadian and ultradian rhythmicity to per0 and per- mutants.
P-element-mediated transformations involving DNA fragments from the period (per) clock gene of Drosophila melanogaster have shown that several subsegments of the locus restore rhythmicity to per0 or
Molecular genetics of a biological clock in Drosophila.
  • T. Bargiello, M. W. Young
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1984
TLDR
Physical characterization of a series of chromosomal rearrangements altering per locus activity indicates that DNA affecting behavioral rhythms is found in a 7.1-kb HindIII fragment.
P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic drosophila melanogaster
TLDR
Certain subsegments of the per region, transduced into the genome of arrhythmic pero flies, restore rhythmicity in circadian locomotor behavior and the male's courtship song.
The period clock locus of D. melanogaster codes for a proteoglycan
TLDR
To determine whether the per transcript codes for a proteoglycan, a region of its coding sequence was expressed (in bacteria) as part of a fusion protein, which was used to immunize rabbits and detected an antigen that is present in wild-type flies and absent in a per- mutant.
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