Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1998 May;149(1):165–178. doi: 10.1093/genetics/149.1.165

Molecular and behavioral analysis of four period mutants in Drosophila melanogaster encompassing extreme short, novel long, and unorthodox arrhythmic types.

M J Hamblen 1, N E White 1, P T Emery 1, K Kaiser 1, J C Hall 1
PMCID: PMC1460118  PMID: 9584094

Abstract

Of the mutationally defined rhythm genes in Drosophila melanogaster, period (per) has been studied the most. We have molecularly characterized three older per mutants-perT, perClk, and per04-along with a novel long-period one (perSLIH). Each mutant is the result of a single nucleotide change. perT, perClk, and perSLIH are accounted for by amino acid substitutions; per04 is altered at a splice site acceptor and causes aberrant splicing. perSLIH exhibits a long period of 27 hr in constant darkness and entrains to light/dark (L/D) cycles with a later-than-normal evening peak of locomotion. perSLIH males are more rhythmic than females. perSLIH's clock runs faster at higher temperatures and slower at lower ones, exhibiting a temperature-compensation defect opposite to that of perLong. The per-encoded protein (PER) in the perT mutant cycles in L/D with an earlier-than-normal peak; this peak in perSLIH is later than normal, and there was a slight difference in the PER timecourse of males vs. females. PER in per04 was undetectable. Two of these mutations, perSLIH and perClk, lie within regions of PER that have not been studied previously and may define important functional domains of this clock protein.

Full Text

The Full Text of this article is available as a PDF (319.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson B. D., Johnson K. A., Dunlap J. C. Circadian clock locus frequency: protein encoded by a single open reading frame defines period length and temperature compensation. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7683–7687. doi: 10.1073/pnas.91.16.7683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baylies M. K., Bargiello T. A., Jackson F. R., Young M. W. Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock. 1987 Mar 26-Apr 1Nature. 326(6111):390–392. doi: 10.1038/326390a0. [DOI] [PubMed] [Google Scholar]
  3. Citri Y., Colot H. V., Jacquier A. C., Yu Q., Hall J. C., Baltimore D., Rosbash M. A family of unusually spliced biologically active transcripts encoded by a Drosophila clock gene. Nature. 1987 Mar 5;326(6108):42–47. doi: 10.1038/326042a0. [DOI] [PubMed] [Google Scholar]
  4. Collier V. L., Kronert W. A., O'Donnell P. T., Edwards K. A., Bernstein S. I. Alternative myosin hinge regions are utilized in a tissue-specific fashion that correlates with muscle contraction speed. Genes Dev. 1990 Jun;4(6):885–895. doi: 10.1101/gad.4.6.885. [DOI] [PubMed] [Google Scholar]
  5. Colot H. V., Hall J. C., Rosbash M. Interspecific comparison of the period gene of Drosophila reveals large blocks of non-conserved coding DNA. EMBO J. 1988 Dec 1;7(12):3929–3937. doi: 10.1002/j.1460-2075.1988.tb03279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coté G. G., Brody S. Circadian rhythms in Drosophila melanogaster: analysis of period as a function of gene dosage at the per (period) locus. J Theor Biol. 1986 Aug 21;121(4):487–503. doi: 10.1016/s0022-5193(86)80104-7. [DOI] [PubMed] [Google Scholar]
  7. Curtin K. D., Huang Z. J., Rosbash M. Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock. Neuron. 1995 Feb;14(2):365–372. doi: 10.1016/0896-6273(95)90292-9. [DOI] [PubMed] [Google Scholar]
  8. Dowse H. B., Ringo J. M. Further evidence that the circadian clock in Drosophila is a population of coupled ultradian oscillators. J Biol Rhythms. 1987 Spring;2(1):65–76. doi: 10.1177/074873048700200106. [DOI] [PubMed] [Google Scholar]
  9. Dunlap J. C., Feldman J. F. On the role of protein synthesis in the circadian clock of Neurospora crassa. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1096–1100. doi: 10.1073/pnas.85.4.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dunlap J. C. Genetics and molecular analysis of circadian rhythms. Annu Rev Genet. 1996;30:579–601. doi: 10.1146/annurev.genet.30.1.579. [DOI] [PubMed] [Google Scholar]
  11. Dushay M. S., Konopka R. J., Orr D., Greenacre M. L., Kyriacou C. P., Rosbash M., Hall J. C. Phenotypic and genetic analysis of Clock, a new circadian rhythm mutant in Drosophila melanogaster. Genetics. 1990 Jul;125(3):557–578. doi: 10.1093/genetics/125.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Edery I., Zwiebel L. J., Dembinska M. E., Rosbash M. Temporal phosphorylation of the Drosophila period protein. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2260–2264. doi: 10.1073/pnas.91.6.2260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ewer J., Frisch B., Hamblen-Coyle M. J., Rosbash M., Hall J. C. Expression of the period clock gene within different cell types in the brain of Drosophila adults and mosaic analysis of these cells' influence on circadian behavioral rhythms. J Neurosci. 1992 Sep;12(9):3321–3349. doi: 10.1523/JNEUROSCI.12-09-03321.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ewer J., Hamblen-Coyle M., Rosbash M., Hall J. C. Requirement for period gene expression in the adult and not during development for locomotor activity rhythms of imaginal Drosophila melanogaster. J Neurogenet. 1990 Nov;7(1):31–73. doi: 10.3109/01677069009084151. [DOI] [PubMed] [Google Scholar]
  15. Fletcher C. F., Lutz C. M., O'Sullivan T. N., Shaughnessy J. D., Jr, Hawkes R., Frankel W. N., Copeland N. G., Jenkins N. A. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell. 1996 Nov 15;87(4):607–617. doi: 10.1016/s0092-8674(00)81381-1. [DOI] [PubMed] [Google Scholar]
  16. Frisch B., Hardin P. E., Hamblen-Coyle M. J., Rosbash M., Hall J. C. A promoterless period gene mediates behavioral rhythmicity and cyclical per expression in a restricted subset of the Drosophila nervous system. Neuron. 1994 Mar;12(3):555–570. doi: 10.1016/0896-6273(94)90212-7. [DOI] [PubMed] [Google Scholar]
  17. Gailey D. A., Villella A., Tully T. Reassessment of the effect of biological rhythm mutations on learning in Drosophila melanogaster. J Comp Physiol A. 1991 Dec;169(6):685–697. doi: 10.1007/BF00194897. [DOI] [PubMed] [Google Scholar]
  18. Garceau N. Y., Liu Y., Loros J. J., Dunlap J. C. Alternative initiation of translation and time-specific phosphorylation yield multiple forms of the essential clock protein FREQUENCY. Cell. 1997 May 2;89(3):469–476. doi: 10.1016/s0092-8674(00)80227-5. [DOI] [PubMed] [Google Scholar]
  19. Gardner G. F., Feldman J. F. Temperature Compensation of Circadian Period Length in Clock Mutants of Neurospora crassa. Plant Physiol. 1981 Dec;68(6):1244–1248. doi: 10.1104/pp.68.6.1244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hamblen-Coyle M., Konopka R. J., Zwiebel L. J., Colot H. V., Dowse H. B., Rosbash M., Hall J. C. A new mutation at the period locus of Drosophila melanogaster with some novel effects on circadian rhythms. J Neurogenet. 1989 Aug;5(4):229–256. doi: 10.3109/01677068909066210. [DOI] [PubMed] [Google Scholar]
  21. Hamblen M., Zehring W. A., Kyriacou C. P., Reddy P., Yu Q., Wheeler D. A., Zwiebel L. J., Konopka R. J., Rosbash M., Hall J. C. 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. J Neurogenet. 1986 Sep;3(5):249–291. doi: 10.3109/01677068609106855. [DOI] [PubMed] [Google Scholar]
  22. Iwasaki K., Thomas J. H. Genetics in rhythm. Trends Genet. 1997 Mar;13(3):111–115. doi: 10.1016/s0168-9525(97)01059-7. [DOI] [PubMed] [Google Scholar]
  23. Kay S. A., Millar A. J. New models in vogue for circadian clocks. Cell. 1995 Nov 3;83(3):361–364. doi: 10.1016/0092-8674(95)90113-2. [DOI] [PubMed] [Google Scholar]
  24. King D. P., Zhao Y., Sangoram A. M., Wilsbacher L. D., Tanaka M., Antoch M. P., Steeves T. D., Vitaterna M. H., Kornhauser J. M., Lowrey P. L. Positional cloning of the mouse circadian clock gene. Cell. 1997 May 16;89(4):641–653. doi: 10.1016/s0092-8674(00)80245-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Konopka R. J., Hamblen-Coyle M. J., Jamison C. F., Hall J. C. An ultrashort clock mutation at the period locus of Drosophila melanogaster that reveals some new features of the fly's circadian system. J Biol Rhythms. 1994 Winter;9(3-4):189–216. doi: 10.1177/074873049400900303. [DOI] [PubMed] [Google Scholar]
  26. Konopka R. J., Pittendrigh C., Orr D. Reciprocal behaviour associated with altered homeostasis and photosensitivity of Drosophila clock mutants. J Neurogenet. 1989 Sep;6(1):1–10. doi: 10.3109/01677068909107096. [DOI] [PubMed] [Google Scholar]
  27. Krawczak M., Reiss J., Cooper D. N. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet. 1992 Sep-Oct;90(1-2):41–54. doi: 10.1007/BF00210743. [DOI] [PubMed] [Google Scholar]
  28. Levy L. S., Manning J. E. Messenger RNA sequence complexity and homology in developmental stages of Drosophila. Dev Biol. 1981 Jul 15;85(1):141–149. doi: 10.1016/0012-1606(81)90243-8. [DOI] [PubMed] [Google Scholar]
  29. Lichtinghagen R., Stocker M., Wittka R., Boheim G., Stühmer W., Ferrus A., Pongs O. Molecular basis of altered excitability in Shaker mutants of Drosophila melanogaster. EMBO J. 1990 Dec;9(13):4399–4407. doi: 10.1002/j.1460-2075.1990.tb07890.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lorenz L. J., Hall J. C., Rosbash M. Expression of a Drosophila mRNA is under circadian clock control during pupation. Development. 1989 Dec;107(4):869–880. doi: 10.1242/dev.107.4.869. [DOI] [PubMed] [Google Scholar]
  31. Loros J. J., Feldman J. F. Loss of temperature compensation of circadian period length in the frq-9 mutant of Neurospora crassa. J Biol Rhythms. 1986 Fall;1(3):187–198. doi: 10.1177/074873048600100302. [DOI] [PubMed] [Google Scholar]
  32. Marrus S. B., Zeng H., Rosbash M. Effect of constant light and circadian entrainment of perS flies: evidence for light-mediated delay of the negative feedback loop in Drosophila. EMBO J. 1996 Dec 16;15(24):6877–6886. [PMC free article] [PubMed] [Google Scholar]
  33. Reddy P., Zehring W. A., Wheeler D. A., Pirrotta V., Hadfield C., Hall J. C., Rosbash M. Molecular analysis of the period locus in Drosophila melanogaster and identification of a transcript involved in biological rhythms. Cell. 1984 Oct;38(3):701–710. doi: 10.1016/0092-8674(84)90265-4. [DOI] [PubMed] [Google Scholar]
  34. Rosato E., Piccin A., Kyriacou C. P. Circadian rhythms: from behaviour to molecules. Bioessays. 1997 Dec;19(12):1075–1082. doi: 10.1002/bies.950191206. [DOI] [PubMed] [Google Scholar]
  35. Rutila J. E., Edery I., Hall J. C., Rosbash M. The analysis of new short-period circadian rhythm mutants suggests features of D. melanogaster period gene function. J Neurogenet. 1992 May;8(2):101–113. doi: 10.3109/01677069209084155. [DOI] [PubMed] [Google Scholar]
  36. Rutila J. E., Zeng H., Le M., Curtin K. D., Hall J. C., Rosbash M. The timSL mutant of the Drosophila rhythm gene timeless manifests allele-specific interactions with period gene mutants. Neuron. 1996 Nov;17(5):921–929. doi: 10.1016/s0896-6273(00)80223-8. [DOI] [PubMed] [Google Scholar]
  37. Saez L., Young M. W. Regulation of nuclear entry of the Drosophila clock proteins period and timeless. Neuron. 1996 Nov;17(5):911–920. doi: 10.1016/s0896-6273(00)80222-6. [DOI] [PubMed] [Google Scholar]
  38. Sawyer L. A., Hennessy J. M., Peixoto A. A., Rosato E., Parkinson H., Costa R., Kyriacou C. P. Natural variation in a Drosophila clock gene and temperature compensation. Science. 1997 Dec 19;278(5346):2117–2120. doi: 10.1126/science.278.5346.2117. [DOI] [PubMed] [Google Scholar]
  39. Siwicki K. K., Eastman C., Petersen G., Rosbash M., Hall J. C. Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system. Neuron. 1988 Apr;1(2):141–150. doi: 10.1016/0896-6273(88)90198-5. [DOI] [PubMed] [Google Scholar]
  40. Stanewsky R., Frisch B., Brandes C., Hamblen-Coyle M. J., Rosbash M., Hall J. C. Temporal and spatial expression patterns of transgenes containing increasing amounts of the Drosophila clock gene period and a lacZ reporter: mapping elements of the PER protein involved in circadian cycling. J Neurosci. 1997 Jan 15;17(2):676–696. doi: 10.1523/JNEUROSCI.17-02-00676.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Taylor W. R. The classification of amino acid conservation. J Theor Biol. 1986 Mar 21;119(2):205–218. doi: 10.1016/s0022-5193(86)80075-3. [DOI] [PubMed] [Google Scholar]
  42. Tümer Z., Lund C., Tolshave J., Vural B., Tønnesen T., Horn N. Identification of point mutations in 41 unrelated patients affected with Menkes disease. Am J Hum Genet. 1997 Jan;60(1):63–71. [PMC free article] [PubMed] [Google Scholar]
  43. Wheeler D. A., Hamblen-Coyle M. J., Dushay M. S., Hall J. C. Behavior in light-dark cycles of Drosophila mutants that are arrhythmic, blind, or both. J Biol Rhythms. 1993 Spring;8(1):67–94. doi: 10.1177/074873049300800106. [DOI] [PubMed] [Google Scholar]
  44. Yu C. E., Oshima J., Wijsman E. M., Nakura J., Miki T., Piussan C., Matthews S., Fu Y. H., Mulligan J., Martin G. M. Mutations in the consensus helicase domains of the Werner syndrome gene. Werner's Syndrome Collaborative Group. Am J Hum Genet. 1997 Feb;60(2):330–341. [PMC free article] [PubMed] [Google Scholar]
  45. Yu Q., Colot H. V., Kyriacou C. P., Hall J. C., Rosbash M. Behaviour modification by in vitro mutagenesis of a variable region within the period gene of Drosophila. Nature. 1987 Apr 23;326(6115):765–769. doi: 10.1038/326765a0. [DOI] [PubMed] [Google Scholar]
  46. Yu Q., Jacquier A. C., Citri Y., Hamblen M., Hall J. C., Rosbash M. Molecular mapping of point mutations in the period gene that stop or speed up biological clocks in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1987 Feb;84(3):784–788. doi: 10.1073/pnas.84.3.784. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES