Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Circadian oscillation of a mammalian homologue of the Drosophila period gene

Abstract

Many biochemical, physiological and behavioural processes in organisms ranging from microorganisms to vertebrates exhibit circadian rhythms1. In Drosophila, the gene period (per) is required for the circadian rhythms of locomotor activity and eclosion behaviour2. Oscillation in the levels of per mRNA and Period (dPer) protein in the fly brain is thought to be responsible for the rhythmicity3,4. However, no per homologues in animals other than insects have been identified. Here we identify the human and mouse genes (hPER and mPer, respectively) encoding PAS-domain (PAS, a dimerization domain present in Per, Amt and Sim)-containing polypeptides that are highly homologous to dPer. Besides this structural resemblance, mPer shows autonomous circadian oscillation in its expression in the suprachiasmatic nucleus, which is the primary circadian pacemaker in the mammalian brain5,6. Clock, a mammalian clock gene encoding a PAS-containing polypeptide7,8, has now been cloned: it is likely that the Per homologues dimerize with other molecule(s) such as Clock through PAS–PAS interaction in the circadian clock system.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: IMS–PCR (see Methods).
Figure 2: Amino-acid sequence comparisons of the Period family.
Figure 3: Northern blot analysis of hPER and mPer.
Figure 4: Autonomous cycling of mPer mRNA in the mouse SCN.

Similar content being viewed by others

References

  1. Edmunds, L. N. J. Cellular and Molecular Basis of Biological Clocks (Springer, New York, (1988)).

    Google Scholar 

  2. Konopka, R. J. & Benzer, S. Clock mutants of Drosophila melanogaster. Proc. Natl Acad. Sci. USA 68, 2112–2116 (1971).

    Article  ADS  CAS  Google Scholar 

  3. Hardin, P. E., Hall, J. C. & Rosbash, M. Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536–540 (1990).

    Article  ADS  CAS  Google Scholar 

  4. Zerr, D. M., Hall, J. C., Rosbash, M. & Siwicki, K. K. Circadian fluctuations of period protein immunoreactivity in the NS and the visual system of Drosophila. J. Neurosci. 10, 2749–2762 (1990).

    Article  CAS  Google Scholar 

  5. Moore, R. Y. & Eichler, V. B. Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res. 42, 201–216 (1972).

    Article  CAS  Google Scholar 

  6. Stephen, F. K. & Zucker, I. Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc. Natl Acad. Sci. USA 69, 1583–1586 (1972).

    Article  ADS  Google Scholar 

  7. King, D. P. et al. Positional cloning of the mouse circadian Clock gene. Cell 89, 641–653 (1997).

    Article  CAS  Google Scholar 

  8. Antoch, M. P. et al. Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell 89, 655–667 (1997).

    Article  CAS  Google Scholar 

  9. Baylies, M. K., Bargiello, T. A., Jackson, F. R. & Young, M. W. Changes in abundance of structure of the per gene product can alter periodicity of the Drosophila clock. Nature 326, 390–392 (1987).

    Article  ADS  CAS  Google Scholar 

  10. Saez, L. & Young, M. W. Regulation of nuclear entry of the Drosophila clock proteins Period and Timeless. Neuron 17, 911–920 (1996).

    Article  CAS  Google Scholar 

  11. Citri, Y. et al. Afamily of unusually spliced biologically active transcripts encoded by a Drosophila clock gene. Nature 326, 42–47 (1987).

    Article  ADS  CAS  Google Scholar 

  12. Vosshall, L. B., Price, J. L., Sehgal, A., Saez, L. & Young, M. W. Block in nuclear localization of period protein by a second clock mutation, timeless. Science 263, 1606–1609 (1996).

    Article  ADS  Google Scholar 

  13. Huang, Z. J., Curtin, K. D. & Rosbash, M. PER protein interactions and temperature compensation of a circadian clock in Drosophila. Science 267, 1169–1172 (1995).

    Article  ADS  CAS  Google Scholar 

  14. Wheeler, D. A. et al. Molecular transfer of a species-specific behavior from Drosophila simulans and Drosophila melanogaster. Science 251, 1082–1085 (1991).

    Article  ADS  CAS  Google Scholar 

  15. 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. 7, 3929–3937 (1988).

    Article  CAS  Google Scholar 

  16. Reppert, S. M., Tsai, T., Roca, A. L. & Sauman, I. Cloning of a structural and functional homolog of the circadian clock gene period from the giant silkmoth Antheraea pernyi. Neuron 13, 1167–1176 (1994).

    Article  CAS  Google Scholar 

  17. Liu, X., Lorenz, L., Yu, Q., Hall, J. C. & Rosbash, M. Spatial and temporal expression of the period gene in Drosophila melanogaster. Genes Dev. 2, 228–238 (1988).

    Article  CAS  Google Scholar 

  18. Saez, L. & Young, M. W. In situ localization of the per clock protein during development of Drosophila melanogaster. Mol. Cell. Biol. 8, 5378–5385 (1988).

    Article  CAS  Google Scholar 

  19. Inouye, S.-T. & Kawamura, H. Persistence of circadian rhythmicity in a hypothalamic ‘island’ containing the suprachiasmatic nucleus. Proc. Natl Acad. Sci. USA 76, 5962–5966 (1979).

    Article  ADS  CAS  Google Scholar 

  20. Schwarts, W. J. & Gainer, H. Suprachiasmatic nucleus: use of 14C-labeled deoxyglucose uptake as a functional marker. Science 197, 1089–1092 (1977).

    Article  ADS  Google Scholar 

  21. Gillette, M. U. & Reppert, S. M. The hypothalamic suprachiasmatic nuclei: circadian patterns of vasopressin secretion and neuronal activity in vitro. Brain Res. Bull. 19, 135–139 (1987).

    Article  CAS  Google Scholar 

  22. Vitaterna, M. H. et al. Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 264, 719–725 (1994).

    Article  ADS  CAS  Google Scholar 

  23. Ralph, M. R. & Menaker, M. Amutation of the circadian system in golden hamsters. Science 241, 1225–1227 (1988).

    Article  ADS  CAS  Google Scholar 

  24. Ito, T., Hohjoh, H. & Sakaki, Y. Pulse-field polyacrylamide gel electrophoresis: basic phenomena and applications. Electrophoresis 14, 278–282 (1993).

    Article  CAS  Google Scholar 

  25. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning (Cold Spring Harbor Laboratory Press, NY, (1989)).

    Google Scholar 

  26. Church, G. M. & Gilbert, W. Genomic sequencing. Proc. Natl Acad. Sci. USA 81, 1991–1995 (1984).

    Article  ADS  CAS  Google Scholar 

  27. Ban, Y., Shigeyoshi, Y. & Okamura, H. Development of circadian VIP rhythm in the rat suprachiasmatic nucleus. J. Neurosci. 17, 3920–3931 (1997).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank J. Inazawa and M. Hirai for mapping hPER and mPer, respectively; Y.Maebayashi for technical assistance, S.-T. Inouye and M. Hattori for discussion; and D. Yamamoto, R.Ueda, T. Ito and K. Ui-Tei for comments and discussions on the manuscript. This work was partly supported by research grants from the Japanese Ministry of Education, Science, Sports and Culture, and the Japanese Ministry of Health and Welfare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hajime Tei.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tei, H., Okamura, H., Shigeyoshi, Y. et al. Circadian oscillation of a mammalian homologue of the Drosophila period gene. Nature 389, 512–516 (1997). https://doi.org/10.1038/39086

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/39086

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing