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Genetics. Jan 1999; 151(1): 163–175.
PMCID: PMC1460474

The haplolethal region at the 16F gene cluster of Drosophila melanogaster: structure and function.

Abstract

Extensive aneuploid analyses had shown the existence of a few haplolethal (HL) regions and one triplolethal region in the genome of Drosophila melanogaster. Since then, only two haplolethals, 22F1-2 and 16F, have been directly linked to identified genes, dpp and wupA, respectively. However, with the possible exception of dpp, the actual bases for this dosage sensitivity remain unknown. We have generated and characterized dominant-lethal mutations and chromosomal rearrangements in 16F and studied them in relation to the genes in the region. This region extends along 100 kb and includes at least 14 genes. The normal HL function depends on the integrity of a critical 4-kb window of mostly noncoding sequences within the wupA transcription unit that encodes the muscle protein troponin I (TNI). All dominant lethals are breakpoints within that window, which prevent the functional expression of TNI and other adjacent genes in the proximal direction. However, independent mutations in these genes result in recessive lethal phenotypes only. We propose that the HL at 16F represents a long-range cis regulatory region that acts upon a number of functionally related genes whose combined haploidy would yield the dominant-lethal effect.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barbas JA, Galceran J, Torroja L, Prado A, Ferrús A. Abnormal muscle development in the heldup3 mutant of Drosophila melanogaster is caused by a splicing defect affecting selected troponin I isoforms. Mol Cell Biol. 1993 Mar;13(3):1433–1439. [PMC free article] [PubMed]
  • Baumann A, Krah-Jentgens I, Müller R, Müller-Holtkamp F, Seidel R, Kecskemethy N, Casal J, Ferrus A, Pongs O. Molecular organization of the maternal effect region of the Shaker complex of Drosophila: characterization of an I(A) channel transcript with homology to vertebrate Na channel. EMBO J. 1987 Nov;6(11):3419–3429. [PMC free article] [PubMed]
  • Beall CJ, Fyrberg E. Muscle abnormalities in Drosophila melanogaster heldup mutants are caused by missing or aberrant troponin-I isoforms. J Cell Biol. 1991 Sep;114(5):941–951. [PMC free article] [PubMed]
  • Bione S, Tamanini F, Maestrini E, Tribioli C, Poustka A, Torri G, Rivella S, Toniolo D. Transcriptional organization of a 450-kb region of the human X chromosome in Xq28. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10977–10981. [PMC free article] [PubMed]
  • Poulain C, Ferrús A, Mallart A. Modulation of type A K+ current in Drosophila larval muscle by internal Ca2+; effects of the overexpression of frequenin. Pflugers Arch. 1994 May;427(1-2):71–79. [PubMed]
  • Breen TR, Lucchesi JC. Analysis of the dosage compensation of a specific transcript in Drosophila melanogaster. Genetics. 1986 Mar;112(3):483–491. [PMC free article] [PubMed]
  • Chen CN, Malone T, Beckendorf SK, Davis RL. At least two genes reside within a large intron of the dunce gene of Drosophila. Nature. 1987 Oct 22;329(6141):721–724. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Decker CJ, Parker R. Diversity of cytoplasmic functions for the 3' untranslated region of eukaryotic transcripts. Curr Opin Cell Biol. 1995 Jun;7(3):386–392. [PubMed]
  • Dernburg AF, Broman KW, Fung JC, Marshall WF, Philips J, Agard DA, Sedat JW. Perturbation of nuclear architecture by long-distance chromosome interactions. Cell. 1996 May 31;85(5):745–759. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Dorer DR, Christensen AC. The unusual spectrum of mutations induced by hybrid dysgenesis at the Triplo-lethal locus of Drosophila melanogaster. Genetics. 1990 Aug;125(4):795–801. [PMC free article] [PubMed]
  • Dorer DR, Cadden MA, Gordesky-Gold B, Harries G, Christensen AC. Suppression of a lethal trisomic phenotype in Drosophila melanogaster by increased dosage of an unlinked locus. Genetics. 1993 May;134(1):243–249. [PMC free article] [PubMed]
  • Dorer DR, Ezekiel DH, Christensen AC. The Triplo-lethal locus of Drosophila: reexamination of mutants and discovery of a second-site suppressor. Genetics. 1995 Nov;141(3):1037–1042. [PMC free article] [PubMed]
  • Eberl DF, Perkins LA, Engelstein M, Hilliker AJ, Perrimon N. Genetic and developmental analysis of polytene section 17 of the X chromosome of Drosophila melanogaster. Genetics. 1992 Mar;130(3):569–583. [PMC free article] [PubMed]
  • Edwards KA, Chang XJ, Kiehart DP. Essential light chain of Drosophila nonmuscle myosin II. J Muscle Res Cell Motil. 1995 Oct;16(5):491–498. [PubMed]
  • Epstein HF, Bernstein SI. Genetic approaches to understanding muscle development. Dev Biol. 1992 Dec;154(2):231–244. [PubMed]
  • Ferrús A, Llamazares S, de la Pompa JL, Tanouye MA, Pongs O. Genetic analysis of the Shaker gene complex of Drosophila melanogaster. Genetics. 1990 Jun;125(2):383–398. [PMC free article] [PubMed]
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
  • Hiraoka Y, Dernburg AF, Parmelee SJ, Rykowski MC, Agard DA, Sedat JW. The onset of homologous chromosome pairing during Drosophila melanogaster embryogenesis. J Cell Biol. 1993 Feb;120(3):591–600. [PMC free article] [PubMed]
  • Homyk T, Jr, Emerson CP., Jr Functional interactions between unlinked muscle genes within haploinsufficient regions of the Drosophila genome. Genetics. 1988 May;119(1):105–121. [PMC free article] [PubMed]
  • Baker BS, Gorman M, Marín I. Dosage compensation in Drosophila. Annu Rev Genet. 1994;28:491–521. [PubMed]
  • Hong CS, Ganetzky B. Molecular characterization of neurally expressing genes in the para sodium channel gene cluster of drosophila. Genetics. 1996 Mar;142(3):879–892. [PMC free article] [PubMed]
  • Barbas JA, Galceran J, Krah-Jentgens I, de la Pompa JL, Canal I, Pongs O, Ferrús A. Troponin I is encoded in the haplolethal region of the Shaker gene complex of Drosophila. Genes Dev. 1991 Jan;5(1):132–140. [PubMed]
  • Reuter G, Spierer P. Position effect variegation and chromatin proteins. Bioessays. 1992 Sep;14(9):605–612. [PubMed]
  • Rivier DH, Pillus L. Silencing speaks up. Cell. 1994 Mar 25;76(6):963–966. [PubMed]
  • Kamb A, Iverson LE, Tanouye MA. Molecular characterization of Shaker, a Drosophila gene that encodes a potassium channel. Cell. 1987 Jul 31;50(3):405–413. [PubMed]
  • Roehrdanz RL, Lucchesi JC. Mutational Events in the Triplo- and Haplo-Lethal Region (83de) of the DROSOPHILA MELANOGASTER Genome. Genetics. 1980 Jun;95(2):355–366. [PMC free article] [PubMed]
  • Keppy DO, Denell RE. A mutational analysis of the triplo-lethal region of Drosophila melanogaster. Genetics. 1979 Mar;91(3):421–441. [PMC free article] [PubMed]
  • Klemenz R, Weber U, Gehring WJ. The white gene as a marker in a new P-element vector for gene transfer in Drosophila. Nucleic Acids Res. 1987 May 26;15(10):3947–3959. [PMC free article] [PubMed]
  • Spradling AC, Rubin GM. Transposition of cloned P elements into Drosophila germ line chromosomes. Science. 1982 Oct 22;218(4570):341–347. [PubMed]
  • Kuroda MI, Kernan MJ, Kreber R, Ganetzky B, Baker BS. The maleless protein associates with the X chromosome to regulate dosage compensation in Drosophila. Cell. 1991 Sep 6;66(5):935–947. [PubMed]
  • L'Ecuyer TJ, Tompach PC, Morris E, Fulton AB. Transdifferentiation of chicken embryonic cells into muscle cells by the 3' untranslated region of muscle tropomyosin. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7520–7524. [PMC free article] [PubMed]
  • St Johnston RD, Hoffmann FM, Blackman RK, Segal D, Grimaila R, Padgett RW, Irick HA, Gelbart WM. Molecular organization of the decapentaplegic gene in Drosophila melanogaster. Genes Dev. 1990 Jul;4(7):1114–1127. [PubMed]
  • Stossel TP. On the crawling of animal cells. Science. 1993 May 21;260(5111):1086–1094. [PubMed]
  • Lefevre G, Johnson TK. Evidence for a Sex-Linked Haplo-Inviable Locus in the Cut-Singed Region of DROSOPHILA MELANOGASTER. Genetics. 1973 Aug;74(4):633–645. [PMC free article] [PubMed]
  • Tanouye MA, Ferrus A, Fujita SC. Abnormal action potentials associated with the Shaker complex locus of Drosophila. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6548–6552. [PMC free article] [PubMed]
  • Lifschytz E, Green MM. Genetic identification of dominant overproducing mutations: the Beadex gene. Mol Gen Genet. 1979 Mar 20;171(2):153–159. [PubMed]
  • Tejedor F, Zhu XR, Kaltenbach E, Ackermann A, Baumann A, Canal I, Heisenberg M, Fischbach KF, Pongs O. minibrain: a new protein kinase family involved in postembryonic neurogenesis in Drosophila. Neuron. 1995 Feb;14(2):287–301. [PubMed]
  • Lin H, Yutzey KE, Konieczny SF. Muscle-specific expression of the troponin I gene requires interactions between helix-loop-helix muscle regulatory factors and ubiquitous transcription factors. Mol Cell Biol. 1991 Jan;11(1):267–280. [PMC free article] [PubMed]
  • Tempel BL, Papazian DM, Schwarz TL, Jan YN, Jan LY. Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. Science. 1987 Aug 14;237(4816):770–775. [PubMed]
  • Thomas GH, Newbern EC, Korte CC, Bales MA, Muse SV, Clark AG, Kiehart DP. Intragenic duplication and divergence in the spectrin superfamily of proteins. Mol Biol Evol. 1997 Dec;14(12):1285–1295. [PubMed]
  • Lindsley DL, Sandler L, Baker BS, Carpenter AT, Denell RE, Hall JC, Jacobs PA, Miklos GL, Davis BK, Gethmann RC, et al. Segmental aneuploidy and the genetic gross structure of the Drosophila genome. Genetics. 1972 May;71(1):157–184. [PMC free article] [PubMed]
  • Maleszka R, de Couet HG, Miklos GL. Data transferability from model organisms to human beings: insights from the functional genomics of the flightless region of Drosophila. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3731–3736. [PMC free article] [PubMed]
  • Tycowski KT, Shu MD, Steitz JA. A mammalian gene with introns instead of exons generating stable RNA products. Nature. 1996 Feb 1;379(6564):464–466. [PubMed]
  • Nikovits W, Jr, Mar JH, Ordahl CP. Muscle-specific activity of the skeletal troponin I promoter requires interaction between upstream regulatory sequences and elements contained within the first transcribed exon. Mol Cell Biol. 1990 Jul;10(7):3468–3482. [PMC free article] [PubMed]
  • Wharton K, Ray RP, Findley SD, Duncan HE, Gelbart WM. Molecular lesions associated with alleles of decapentaplegic identify residues necessary for TGF-beta/BMP cell signaling in Drosophila melanogaster. Genetics. 1996 Feb;142(2):493–505. [PMC free article] [PubMed]
  • Williamson RM, Hetherington J, Jackson JH. Detection of fundamental principles and a level of order for large-scale gene clustering on the Escherichia coli chromosome. J Mol Evol. 1993 Apr;36(4):347–360. [PubMed]
  • Padgett RW, St Johnston RD, Gelbart WM. A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-beta family. Nature. 1987 Jan 1;325(6099):81–84. [PubMed]
  • Wilson C, Bellen HJ, Gehring WJ. Position effects on eukaryotic gene expression. Annu Rev Cell Biol. 1990;6:679–714. [PubMed]
  • Wright TR. The Wilhelmine E. Key 1992 Invitational lecture. Phenotypic analysis of the Dopa decarboxylase gene cluster mutants in Drosophila melanogaster. J Hered. 1996 May-Jun;87(3):175–190. [PubMed]
  • Young PE, Richman AM, Ketchum AS, Kiehart DP. Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function. Genes Dev. 1993 Jan;7(1):29–41. [PubMed]
  • Pongs O, Lindemeier J, Zhu XR, Theil T, Engelkamp D, Krah-Jentgens I, Lambrecht HG, Koch KW, Schwemer J, Rivosecchi R, et al. Frequenin--a novel calcium-binding protein that modulates synaptic efficacy in the Drosophila nervous system. Neuron. 1993 Jul;11(1):15–28. [PubMed]
  • Yutzey KE, Konieczny SF. Different E-box regulatory sequences are functionally distinct when placed within the context of the troponin I enhancer. Nucleic Acids Res. 1992 Oct 11;20(19):5105–5113. [PMC free article] [PubMed]
  • Yutzey KE, Kline RL, Konieczny SF. An internal regulatory element controls troponin I gene expression. Mol Cell Biol. 1989 Apr;9(4):1397–1405. [PMC free article] [PubMed]
  • Prado A, Canal I, Barbas JA, Molloy J, Ferrús A. Functional recovery of troponin I in a Drosophila heldup mutant after a second site mutation. Mol Biol Cell. 1995 Nov;6(11):1433–1441. [PMC free article] [PubMed]

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