Abstract
The Drosophila melanogaster Gart gene encodes three enzymatic activities in the pathway for purine de novo synthesis. Alternative processing of the primary transcript leads to the synthesis of two overlapping polypeptides. The coding sequence for both polypeptides is interrupted by an intron that contains a functional cuticle protein gene encoded on the opposite DNA strand. Here we show that this nested organization also exists at the homologous locus of a distantly related species, Drosophila pseudoobscura. In both species, the intronic cuticle gene is expressed in wandering larvae and in prepupae. Remarkably, there are 24 different highly conserved noncoding segments within the intron containing the cuticle gene. These are found upstream of the transcriptional start, at the 3' end, and even within the single intronic gene intron. Other introns in the purine gene, including the intron at which alternative processing occurs, show no such homologies. It seems likely that at least some of the conserved noncoding regions are involved in specifying the high level developmental expression of the cuticle gene. We discuss the possibility that shared cis-acting regulatory sites might enhance transcription of both genes and help explain their nested arrangement.
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- Adelman J. P., Bond C. T., Douglass J., Herbert E. Two mammalian genes transcribed from opposite strands of the same DNA locus. Science. 1987 Mar 20;235(4795):1514–1517. doi: 10.1126/science.3547652. [DOI] [PubMed] [Google Scholar]
- Blackman R. K., Meselson M. Interspecific nucleotide sequence comparisons used to identify regulatory and structural features of the Drosophila hsp82 gene. J Mol Biol. 1986 Apr 20;188(4):499–515. doi: 10.1016/s0022-2836(86)80001-8. [DOI] [PubMed] [Google Scholar]
- Britten R. J. Rates of DNA sequence evolution differ between taxonomic groups. Science. 1986 Mar 21;231(4744):1393–1398. doi: 10.1126/science.3082006. [DOI] [PubMed] [Google Scholar]
- Broker T. R., Chow L. T., Dunn A. R., Gelinas R. E., Hassell J. A., Klessig D. F., Lewis J. B., Roberts R. J., Zain B. S. Adenovirus-2 messengers--an example of baroque molecular architecture. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 1):531–553. doi: 10.1101/sqb.1978.042.01.056. [DOI] [PubMed] [Google Scholar]
- 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]
- Garbe J. C., Bendena W. G., Alfano M., Pardue M. L. A Drosophila heat shock locus with a rapidly diverging sequence but a conserved structure. J Biol Chem. 1986 Dec 25;261(36):16889–16894. [PubMed] [Google Scholar]
- Henikoff S., Keene M. A., Fechtel K., Fristrom J. W. Gene within a gene: nested Drosophila genes encode unrelated proteins on opposite DNA strands. Cell. 1986 Jan 17;44(1):33–42. doi: 10.1016/0092-8674(86)90482-4. [DOI] [PubMed] [Google Scholar]
- Henikoff S., Kelly J. D., Cohen E. H. Transcription terminates in yeast distal to a control sequence. Cell. 1983 Jun;33(2):607–614. doi: 10.1016/0092-8674(83)90441-5. [DOI] [PubMed] [Google Scholar]
- Henikoff S., Meselson M. Transcription at two heat shock loci in Drosophila. Cell. 1977 Oct;12(2):441–451. doi: 10.1016/0092-8674(77)90120-9. [DOI] [PubMed] [Google Scholar]
- Henikoff S., Nash D., Hards R., Bleskan J., Woolford J. F., Naguib F., Patterson D. Two Drosophila melanogaster mutations block successive steps of de novo purine synthesis. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3919–3923. doi: 10.1073/pnas.83.11.3919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hiromi Y., Kuroiwa A., Gehring W. J. Control elements of the Drosophila segmentation gene fushi tarazu. Cell. 1985 Dec;43(3 Pt 2):603–613. doi: 10.1016/0092-8674(85)90232-6. [DOI] [PubMed] [Google Scholar]
- Hultmark D., Klemenz R., Gehring W. J. Translational and transcriptional control elements in the untranslated leader of the heat-shock gene hsp22. Cell. 1986 Feb 14;44(3):429–438. doi: 10.1016/0092-8674(86)90464-2. [DOI] [PubMed] [Google Scholar]
- Kassis J. A., Poole S. J., Wright D. K., O'Farrell P. H. Sequence conservation in the protein coding and intron regions of the engrailed transcription unit. EMBO J. 1986 Dec 20;5(13):3583–3589. doi: 10.1002/j.1460-2075.1986.tb04686.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kmiec E. B., Holloman W. K. Homologous pairing of DNA molecules by Ustilago rec1 protein is promoted by sequences of Z-DNA. Cell. 1986 Feb 28;44(4):545–554. doi: 10.1016/0092-8674(86)90264-3. [DOI] [PubMed] [Google Scholar]
- Lee C. S., Curtis D., McCarron M., Love C., Gray M., Bender W., Chovnick A. Mutations affecting expression of the rosy locus in Drosophila melanogaster. Genetics. 1987 May;116(1):55–66. doi: 10.1093/genetics/116.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pardue M. L., Lowenhaupt K., Rich A., Nordheim A. (dC-dA)n.(dG-dT)n sequences have evolutionarily conserved chromosomal locations in Drosophila with implications for roles in chromosome structure and function. EMBO J. 1987 Jun;6(6):1781–1789. doi: 10.1002/j.1460-2075.1987.tb02431.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pirrotta V., Steller H., Bozzetti M. P. Multiple upstream regulatory elements control the expression of the Drosophila white gene. EMBO J. 1985 Dec 16;4(13A):3501–3508. doi: 10.1002/j.1460-2075.1985.tb04109.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reed R., Maniatis T. A role for exon sequences and splice-site proximity in splice-site selection. Cell. 1986 Aug 29;46(5):681–690. doi: 10.1016/0092-8674(86)90343-0. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Snyder M., Hirsh J., Davidson N. The cuticle genes of drosophila: a developmentally regulated gene cluster. Cell. 1981 Jul;25(1):165–177. doi: 10.1016/0092-8674(81)90241-5. [DOI] [PubMed] [Google Scholar]
- Snyder M., Hunkapiller M., Yuen D., Silvert D., Fristrom J., Davidson N. Cuticle protein genes of Drosophila: structure, organization and evolution of four clustered genes. Cell. 1982 Jul;29(3):1027–1040. doi: 10.1016/0092-8674(82)90466-4. [DOI] [PubMed] [Google Scholar]
- Spencer C. A., Gietz R. D., Hodgetts R. B. Overlapping transcription units in the dopa decarboxylase region of Drosophila. Nature. 1986 Jul 17;322(6076):279–281. doi: 10.1038/322279a0. [DOI] [PubMed] [Google Scholar]
- Südhof T. C., Goldstein J. L., Brown M. S., Russell D. W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815–822. doi: 10.1126/science.2988123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams T., Fried M. A mouse locus at which transcription from both DNA strands produces mRNAs complementary at their 3' ends. Nature. 1986 Jul 17;322(6076):275–279. doi: 10.1038/322275a0. [DOI] [PubMed] [Google Scholar]