Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Aug 2;91(16):7683–7687. doi: 10.1073/pnas.91.16.7683

Circadian clock locus frequency: protein encoded by a single open reading frame defines period length and temperature compensation.

B D Aronson 1, K A Johnson 1, J C Dunlap 1
PMCID: PMC44466  PMID: 8052643

Abstract

The frequency (frq) locus encodes a key component, a state variable, in a cellular oscillator generating circadian rhythmicity. Two transcripts have been mapped to this region, and data presented here are consistent with the existence of a third transcript. Analysis of cDNA clones and clock mutants from this region focuses attention on one transcript encoding a protein. FRQ, which is a central clock component: (i) mutations in all of the semidominant frq alleles are the result of single amino acid substitutions and map to the open reading frame (ORF) encoding FRQ; (ii) deletion of this ORF, or a frameshift mutation within it, results in a strain with a recessive clock phenotype characterized by the loss of rhythm stability and compensation. Single amino acid substitutions within, or disruption of, this single ORF are thus sufficient to drive major alterations in both period length and temperature compensation, two canonical characteristics of circadian systems. The 989-amino acid FRQ protein species the circadian function of frq in the assembly of the Neurospora biological clock.

Full text

PDF
7683

Images in this article

7684Image
on p.7684
7686Image
on p.7686
7686Image
on p.7686

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., Loros J. J., Dunlap J. C. Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. Science. 1994 Mar 18;263(5153):1578–1584. doi: 10.1126/science.8128244. [DOI] [PubMed] [Google Scholar]
  2. Aronson B. D., Lindgren K. M., Dunlap J. C., Loros J. J. An efficient method for gene disruption in Neurospora crassa. Mol Gen Genet. 1994 Feb;242(4):490–494. doi: 10.1007/BF00281802. [DOI] [PubMed] [Google Scholar]
  3. Bell-Pedersen D., Dunlap J. C., Loros J. J. The Neurospora circadian clock-controlled gene, ccg-2, is allelic to eas and encodes a fungal hydrophobin required for formation of the conidial rodlet layer. Genes Dev. 1992 Dec;6(12A):2382–2394. doi: 10.1101/gad.6.12a.2382. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dunlap J. C. Genetic analysis of circadian clocks. Annu Rev Physiol. 1993;55:683–728. doi: 10.1146/annurev.ph.55.030193.003343. [DOI] [PubMed] [Google Scholar]
  7. Fu Y. H., Marzluf G. A. Metabolic control and autogenous regulation of nit-3, the nitrate reductase structural gene of Neurospora crassa. J Bacteriol. 1988 Feb;170(2):657–661. doi: 10.1128/jb.170.2.657-661.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fuchs R. MacPattern: protein pattern searching on the Apple Macintosh. Comput Appl Biosci. 1991 Jan;7(1):105–106. doi: 10.1093/bioinformatics/7.1.105. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Karlin S., Altschul S. F. Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2264–2268. doi: 10.1073/pnas.87.6.2264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  13. Loros J. J., Denome S. A., Dunlap J. C. Molecular cloning of genes under control of the circadian clock in Neurospora. Science. 1989 Jan 20;243(4889):385–388. doi: 10.1126/science.2563175. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Lüttke A. MacPROT: a set of BASIC programs for protein structure analysis. Comput Methods Programs Biomed. 1990 Feb;31(2):105–112. doi: 10.1016/0169-2607(90)90057-g. [DOI] [PubMed] [Google Scholar]
  16. McClung C. R., Fox B. A., Dunlap J. C. The Neurospora clock gene frequency shares a sequence element with the Drosophila clock gene period. Nature. 1989 Jun 15;339(6225):558–562. doi: 10.1038/339558a0. [DOI] [PubMed] [Google Scholar]
  17. Merrow M. W., Dunlap J. C. Intergeneric complementation of a circadian rhythmicity defect: phylogenetic conservation of structure and function of the clock gene frequency. EMBO J. 1994 May 15;13(10):2257–2266. doi: 10.1002/j.1460-2075.1994.tb06507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Orbach M. J., Sachs M. S., Yanofsky C. The Neurospora crassa arg-2 locus. Structure and expression of the gene encoding the small subunit of arginine-specific carbamoyl phosphate synthetase. J Biol Chem. 1990 Jul 5;265(19):10981–10987. [PubMed] [Google Scholar]
  19. Rihs H. P., Jans D. A., Fan H., Peters R. The rate of nuclear cytoplasmic protein transport is determined by the casein kinase II site flanking the nuclear localization sequence of the SV40 T-antigen. EMBO J. 1991 Mar;10(3):633–639. doi: 10.1002/j.1460-2075.1991.tb07991.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  21. Rokeach L. A., Jannatipour M., Haselby J. A., Hoch S. O. Primary structure of a human small nuclear ribonucleoprotein polypeptide as deduced by cDNA analysis. J Biol Chem. 1989 Mar 25;264(9):5024–5030. [PubMed] [Google Scholar]
  22. Tamaki M., Nakamura E., Nishikubo C., Sakata T., Shin M., Teraoka H. Rat lipocortin I cDNA. Nucleic Acids Res. 1987 Sep 25;15(18):7637–7637. doi: 10.1093/nar/15.18.7637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Uberbacher E. C., Mural R. J. Locating protein-coding regions in human DNA sequences by a multiple sensor-neural network approach. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11261–11265. doi: 10.1073/pnas.88.24.11261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vollmer S. J., Yanofsky C. Efficient cloning of genes of Neurospora crassa. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4869–4873. doi: 10.1073/pnas.83.13.4869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES