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. 1996 Dec;144(4):1653–1664. doi: 10.1093/genetics/144.4.1653

Regulation of the Gene Sex-Lethal: A Comparative Analysis of Drosophila Melanogaster and Drosophila Subobscura

LOF Penalva 1, H Sakamoto 1, A Navarro-Sabate 1, E Sakashita 1, B Granadino 1, C Segarra 1, L Sanchez 1
PMCID: PMC1207716  PMID: 8978052

Abstract

The Drosophila gene Sex-lethal (Sxl) controls the processes of sex determination and dosage compensation. A Drosophila subobscura genomic fragment containing all the exons and the late and early promotors in the Sxl gene of D. melanogaster was isolated. Early Sxl expression in D. subobscura seems to be controlled at the transcriptional level, possibly by the X:A signal. In the region upstream of the early Sxl transcription initiation site are two conserved regions suggested to be involved in the early activation of Sxl. Late Sxl expression in D. subobscura produces four transcripts in adult females and males. In males, the transcripts have an additional exon which contains three translational stop codons so that a truncated, presumably nonfunctional Sxl protein is produced. The Sxl pre-mRNA of D. subobscura lacks the poly-U sequence presented at the polypirimidine tract of the 3' splice site of the male-specific exon present in D. melanogaster. Introns 2 and 3 contain the Sxl-binding poly-U stretches, whose localization in intron 2 varies but in intron 3 is conserved. The Sxl protein is fully conserved at the amino acid level in both species.

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Selected References

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  1. Bachiller D., Sánchez L. Production of X0 clones in XX females of Drosophila. Genet Res. 1991 Feb;57(1):23–28. doi: 10.1017/s0016672300028998. [DOI] [PubMed] [Google Scholar]
  2. Baker B. S., Gorman M., Marín I. Dosage compensation in Drosophila. Annu Rev Genet. 1994;28:491–521. doi: 10.1146/annurev.ge.28.120194.002423. [DOI] [PubMed] [Google Scholar]
  3. Bell L. R., Horabin J. I., Schedl P., Cline T. W. Positive autoregulation of sex-lethal by alternative splicing maintains the female determined state in Drosophila. Cell. 1991 Apr 19;65(2):229–239. doi: 10.1016/0092-8674(91)90157-t. [DOI] [PubMed] [Google Scholar]
  4. Bell L. R., Maine E. M., Schedl P., Cline T. W. Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins. Cell. 1988 Dec 23;55(6):1037–1046. doi: 10.1016/0092-8674(88)90248-6. [DOI] [PubMed] [Google Scholar]
  5. Bopp D., Bell L. R., Cline T. W., Schedl P. Developmental distribution of female-specific Sex-lethal proteins in Drosophila melanogaster. Genes Dev. 1991 Mar;5(3):403–415. doi: 10.1101/gad.5.3.403. [DOI] [PubMed] [Google Scholar]
  6. Bopp D., Calhoun G., Horabin J. I., Samuels M., Schedl P. Sex-specific control of Sex-lethal is a conserved mechanism for sex determination in the genus Drosophila. Development. 1996 Mar;122(3):971–982. doi: 10.1242/dev.122.3.971. [DOI] [PubMed] [Google Scholar]
  7. Cavener D. R. Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates. Nucleic Acids Res. 1987 Feb 25;15(4):1353–1361. doi: 10.1093/nar/15.4.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cline T. W. Autoregulatory functioning of a Drosophila gene product that establish es and maintains the sexually determined state. Genetics. 1984 Jun;107(2):231–277. doi: 10.1093/genetics/107.2.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cline T. W. The Drosophila sex determination signal: how do flies count to two? Trends Genet. 1993 Nov;9(11):385–390. doi: 10.1016/0168-9525(93)90138-8. [DOI] [PubMed] [Google Scholar]
  10. Estes P. A., Keyes L. N., Schedl P. Multiple response elements in the Sex-lethal early promoter ensure its female-specific expression pattern. Mol Cell Biol. 1995 Feb;15(2):904–917. doi: 10.1128/mcb.15.2.904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Granadino B., Campuzano S., Sánchez L. The Drosophila melanogaster fl(2)d gene is needed for the female-specific splicing of Sex-lethal RNA. EMBO J. 1990 Aug;9(8):2597–2602. doi: 10.1002/j.1460-2075.1990.tb07441.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  14. Horabin J. I., Schedl P. Sex-lethal autoregulation requires multiple cis-acting elements upstream and downstream of the male exon and appears to depend largely on controlling the use of the male exon 5' splice site. Mol Cell Biol. 1993 Dec;13(12):7734–7746. doi: 10.1128/mcb.13.12.7734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hoshijima K., Kohyama A., Watakabe I., Inoue K., Sakamoto H., Shimura Y. Transcriptional regulation of the Sex-lethal gene by helix-loop-helix proteins. Nucleic Acids Res. 1995 Sep 11;23(17):3441–3448. doi: 10.1093/nar/23.17.3441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Inoue K., Hoshijima K., Sakamoto H., Shimura Y. Binding of the Drosophila sex-lethal gene product to the alternative splice site of transformer primary transcript. Nature. 1990 Mar 29;344(6265):461–463. doi: 10.1038/344461a0. [DOI] [PubMed] [Google Scholar]
  18. Izaurralde E., Lewis J., McGuigan C., Jankowska M., Darzynkiewicz E., Mattaj I. W. A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell. 1994 Aug 26;78(4):657–668. doi: 10.1016/0092-8674(94)90530-4. [DOI] [PubMed] [Google Scholar]
  19. KUNZE-MUHL E., MULLER E. Weitere Untersuchungen über die chromosomale Struktur und die natürlichen Strukturtypen von Drosophila subobscura Coll. Chromosoma. 1958;9(6):559–570. [PubMed] [Google Scholar]
  20. Kataoka N., Ohno M., Kangawa K., Tokoro Y., Shimura Y. Cloning of a complementary DNA encoding an 80 kilodalton nuclear cap binding protein. Nucleic Acids Res. 1994 Sep 25;22(19):3861–3865. doi: 10.1093/nar/22.19.3861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Keyes L. N., Cline T. W., Schedl P. The primary sex determination signal of Drosophila acts at the level of transcription. Cell. 1992 Mar 6;68(5):933–943. doi: 10.1016/0092-8674(92)90036-c. [DOI] [PubMed] [Google Scholar]
  22. Klemenz R., Hultmark D., Gehring W. J. Selective translation of heat shock mRNA in Drosophila melanogaster depends on sequence information in the leader. EMBO J. 1985 Aug;4(8):2053–2060. doi: 10.1002/j.1460-2075.1985.tb03891.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Montgomery E., Charlesworth B., Langley C. H. A test for the role of natural selection in the stabilization of transposable element copy number in a population of Drosophila melanogaster. Genet Res. 1987 Feb;49(1):31–41. doi: 10.1017/s0016672300026707. [DOI] [PubMed] [Google Scholar]
  24. Mount S. M., Burks C., Hertz G., Stormo G. D., White O., Fields C. Splicing signals in Drosophila: intron size, information content, and consensus sequences. Nucleic Acids Res. 1992 Aug 25;20(16):4255–4262. doi: 10.1093/nar/20.16.4255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Oliver B., Kim Y. J., Baker B. S. Sex-lethal, master and slave: a hierarchy of germ-line sex determination in Drosophila. Development. 1993 Nov;119(3):897–908. doi: 10.1242/dev.119.3.897. [DOI] [PubMed] [Google Scholar]
  26. Oliver B., Perrimon N., Mahowald A. P. Genetic evidence that the sans fille locus is involved in Drosophila sex determination. Genetics. 1988 Sep;120(1):159–171. doi: 10.1093/genetics/120.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Parkhurst S. M., Ish-Horowicz D. Common denominators for sex. Curr Biol. 1992 Dec;2(12):629–631. doi: 10.1016/0960-9822(92)90097-t. [DOI] [PubMed] [Google Scholar]
  28. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Robberson B. L., Cote G. J., Berget S. M. Exon definition may facilitate splice site selection in RNAs with multiple exons. Mol Cell Biol. 1990 Jan;10(1):84–94. doi: 10.1128/mcb.10.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sakamoto H., Inoue K., Higuchi I., Ono Y., Shimura Y. Control of Drosophila Sex-lethal pre-mRNA splicing by its own female-specific product. Nucleic Acids Res. 1992 Nov 11;20(21):5533–5540. doi: 10.1093/nar/20.21.5533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sakashita E., Sakamoto H. Characterization of RNA binding specificity of the Drosophila sex-lethal protein by in vitro ligand selection. Nucleic Acids Res. 1994 Oct 11;22(20):4082–4086. doi: 10.1093/nar/22.20.4082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Salz H. K., Maine E. M., Keyes L. N., Samuels M. E., Cline T. W., Schedl P. The Drosophila female-specific sex-determination gene, Sex-lethal, has stage-, tissue-, and sex-specific RNAs suggesting multiple modes of regulation. Genes Dev. 1989 May;3(5):708–719. doi: 10.1101/gad.3.5.708. [DOI] [PubMed] [Google Scholar]
  33. Salz H. K. The genetic analysis of snf: a Drosophila sex determination gene required for activation of Sex-lethal in both the germline and the soma. Genetics. 1992 Mar;130(3):547–554. doi: 10.1093/genetics/130.3.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Samuels M. E., Bopp D., Colvin R. A., Roscigno R. F., Garcia-Blanco M. A., Schedl P. RNA binding by Sxl proteins in vitro and in vivo. Mol Cell Biol. 1994 Jul;14(7):4975–4990. doi: 10.1128/mcb.14.7.4975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Samuels M. E., Schedl P., Cline T. W. The complex set of late transcripts from the Drosophila sex determination gene sex-lethal encodes multiple related polypeptides. Mol Cell Biol. 1991 Jul;11(7):3584–3602. doi: 10.1128/mcb.11.7.3584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Segarra C., Aguadé M. Nucleotide divergence of the rp49 gene region between Drosophila melanogaster and two species of the Obscura group of Drosophila. J Mol Evol. 1993 Mar;36(3):243–248. doi: 10.1007/BF00160479. [DOI] [PubMed] [Google Scholar]
  38. Singh R., Valcárcel J., Green M. R. Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins. Science. 1995 May 26;268(5214):1173–1176. doi: 10.1126/science.7761834. [DOI] [PubMed] [Google Scholar]
  39. Sosnowski B. A., Belote J. M., McKeown M. Sex-specific alternative splicing of RNA from the transformer gene results from sequence-dependent splice site blockage. Cell. 1989 Aug 11;58(3):449–459. doi: 10.1016/0092-8674(89)90426-1. [DOI] [PubMed] [Google Scholar]
  40. Steinmann-Zwicky M., Amrein H., Nöthiger R. Genetic control of sex determination in Drosophila. Adv Genet. 1990;27:189–237. doi: 10.1016/s0065-2660(08)60026-7. [DOI] [PubMed] [Google Scholar]
  41. Steinmann-Zwicky M. Sex determination in Drosophila: the X-chromosomal gene liz is required for Sxl activity. EMBO J. 1988 Dec 1;7(12):3889–3898. doi: 10.1002/j.1460-2075.1988.tb03275.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sánchez L., Granadino B., Torres M. Sex determination in Drosophila melanogaster: X-linked genes involved in the initial step of sex-lethal activation. Dev Genet. 1994;15(3):251–264. doi: 10.1002/dvg.1020150307. [DOI] [PubMed] [Google Scholar]
  43. Sánchez L., Nöthiger R. Sex determination and dosage compensation in Drosophila melanogaster: production of male clones in XX females. EMBO J. 1983;2(4):485–491. doi: 10.1002/j.1460-2075.1983.tb01451.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tautz D., Pfeifle C. A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma. 1989 Aug;98(2):81–85. doi: 10.1007/BF00291041. [DOI] [PubMed] [Google Scholar]
  45. Torres M., Sánchez L. The sisterless-b function of the Drosophila gene scute is restricted to the stage when the X:A ratio determines the activity of Sex-lethal. Development. 1991 Oct;113(2):715–722. doi: 10.1242/dev.113.2.715. [DOI] [PubMed] [Google Scholar]
  46. Valcárcel J., Singh R., Zamore P. D., Green M. R. The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer pre-mRNA. Nature. 1993 Mar 11;362(6416):171–175. doi: 10.1038/362171a0. [DOI] [PubMed] [Google Scholar]
  47. Younger-Shepherd S., Vaessin H., Bier E., Jan L. Y., Jan Y. N. deadpan, an essential pan-neural gene encoding an HLH protein, acts as a denominator in Drosophila sex determination. Cell. 1992 Sep 18;70(6):911–922. doi: 10.1016/0092-8674(92)90242-5. [DOI] [PubMed] [Google Scholar]

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