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
. 1987 Feb;84(3):784–788. doi: 10.1073/pnas.84.3.784

Molecular mapping of point mutations in the period gene that stop or speed up biological clocks in Drosophila melanogaster.

Q Yu, A C Jacquier, Y Citri, M Hamblen, J C Hall, M Rosbash
PMCID: PMC304300  PMID: 3027703

Abstract

The pero1 and the pers mutations in Drosophila melanogaster, which seem to eliminate or speed up, respectively, the clocks underlying biological rhythmicity, were mapped to single nucleotides. Chimeric DNA fragments consisting of well-defined wild-type plus mutant DNA subsegments were constructed, introduced into flies by germ-line transformation, and assayed for biological activity. These experiments localized both pero1 and pers to a 1.7-kilobase DNA fragment that is mostly coding DNA. Sequencing of this subsegment from each mutant showed that pero1 is completely accounted for by a nonsense mutation in the third coding exon of a 4.5-kilobase RNA transcribed from this locus. The pers mutation is also a single nucleotide substitution, in the fourth coding exon, which results in a serine-to-asparagine substitution in the per gene protein product. The functional significance of these changes is discussed with reference to the phenotypes of the two mutations.

Full text

PDF
784

Images in this article

786Image
on p.786
786Image
on p.786
786Image
on p.786
786Image
on p.786
787Image
on p.787
787Image
on p.787

Selected References

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

  1. Bargiello T. A., Jackson F. R., Young M. W. Restoration of circadian behavioural rhythms by gene transfer in Drosophila. Nature. 1984 Dec 20;312(5996):752–754. doi: 10.1038/312752a0. [DOI] [PubMed] [Google Scholar]
  2. Bargiello T. A., Young M. W. Molecular genetics of a biological clock in Drosophila. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2142–2146. doi: 10.1073/pnas.81.7.2142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bourdon M. A., Oldberg A., Pierschbacher M., Ruoslahti E. Molecular cloning and sequence analysis of a chondroitin sulfate proteoglycan cDNA. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1321–1325. doi: 10.1073/pnas.82.5.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Dente L., Cesareni G., Cortese R. pEMBL: a new family of single stranded plasmids. Nucleic Acids Res. 1983 Mar 25;11(6):1645–1655. doi: 10.1093/nar/11.6.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eckols T. K., Thompson R. E., Masaracchia R. A. Primary substrate specificity determinants for the H4-specific protease-activated protein phosphotransferase. Eur J Biochem. 1983 Aug 1;134(2):249–254. doi: 10.1111/j.1432-1033.1983.tb07558.x. [DOI] [PubMed] [Google Scholar]
  7. Feramisco J. R., Glass D. B., Krebs E. G. Optimal spatial requirements for the location of basic residues in peptide substrates for the cyclic AMP-dependent protein kinase. J Biol Chem. 1980 May 10;255(9):4240–4245. [PubMed] [Google Scholar]
  8. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Jackson F. R., Bargiello T. A., Yun S. H., Young M. W. Product of per locus of Drosophila shares homology with proteoglycans. Nature. 1986 Mar 13;320(6058):185–188. doi: 10.1038/320185a0. [DOI] [PubMed] [Google Scholar]
  11. James A. A., Ewer J., Reddy P., Hall J. C., Rosbash M. Embryonic expression of the period clock gene in the central nervous system of Drosophila melanogaster. EMBO J. 1986 Sep;5(9):2313–2320. doi: 10.1002/j.1460-2075.1986.tb04499.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Konopka R. J., Benzer S. Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2112–2116. doi: 10.1073/pnas.68.9.2112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  14. Reddy P., Jacquier A. C., Abovich N., Petersen G., Rosbash M. The period clock locus of D. melanogaster codes for a proteoglycan. Cell. 1986 Jul 4;46(1):53–61. doi: 10.1016/0092-8674(86)90859-7. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Shin H. S., Bargiello T. A., Clark B. T., Jackson F. R., Young M. W. An unusual coding sequence from a Drosophila clock gene is conserved in vertebrates. Nature. 1985 Oct 3;317(6036):445–448. doi: 10.1038/317445a0. [DOI] [PubMed] [Google Scholar]
  17. Simon J. A., Sutton C. A., Lobell R. B., Glaser R. L., Lis J. T. Determinants of heat shock-induced chromosome puffing. Cell. 1985 Apr;40(4):805–817. doi: 10.1016/0092-8674(85)90340-x. [DOI] [PubMed] [Google Scholar]
  18. Smith R. F., Konopka R. J. Circadian clock phenotypes of chromosome aberrations with a breakpoint at the per locus. Mol Gen Genet. 1981;183(2):243–251. doi: 10.1007/BF00270625. [DOI] [PubMed] [Google Scholar]
  19. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  20. Young M. W., Jackson F. R., Shin H. S., Bargiello T. A. A biological clock in Drosophila. Cold Spring Harb Symp Quant Biol. 1985;50:865–875. doi: 10.1101/sqb.1985.050.01.104. [DOI] [PubMed] [Google Scholar]
  21. Young M. W., Judd B. H. Nonessential Sequences, Genes, and the Polytene Chromosome Bands of DROSOPHILA MELANOGASTER. Genetics. 1978 Apr;88(4):723–742. doi: 10.1093/genetics/88.4.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zehring W. A., Wheeler D. A., Reddy P., Konopka R. J., Kyriacou C. P., Rosbash M., Hall J. C. P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell. 1984 Dec;39(2 Pt 1):369–376. doi: 10.1016/0092-8674(84)90015-1. [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