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. 2001 Aug;158(4):1629–1643. doi: 10.1093/genetics/158.4.1629

The cyclope gene of Drosophila encodes a cytochrome c oxidase subunit VIc homolog.

S Szuplewski 1, R Terracol 1
PMCID: PMC1461756  PMID: 11514451

Abstract

Cytochrome c oxidase is the terminal enzyme of the mitochondrial electron transfer chain. In eukaryotes, the enzyme is composed of 3 mitochondrial DNA-encoded subunits and 7-10 (in mammals) nuclear DNA-encoded subunits. This enzyme has been extensively studied in mammals and yeast but, in Drosophila, very little is known and no mutant has been described so far. Here we report the genetic and molecular characterization of mutations in cyclope (cype) and the cloning of the gene encoding a cytochrome c oxidase subunit VIc homolog. cype is an essential gene whose mutations are lethal and show pleiotropic phenotypes. The 77-amino acid peptide encoded by cype is 46% identical and 59% similar to the human subunit (75 amino acids). The transcripts are expressed maternally and throughout development in localized regions. They are found predominantly in the central nervous system of the embryo; in the central region of imaginal discs; in the germarium, follicular, and nurse cells of the ovary; and in testis. A search in the Genome Annotation Database of Drosophila revealed the absence of subunit VIIb and the presence of 9 putative nuclear cytochrome c oxidase subunits with high identity scores when compared to the 10 human subunits.

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Selected References

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

  1. Adams M. D., Celniker S. E., Holt R. A., Evans C. A., Gocayne J. D., Amanatides P. G., Scherer S. E., Li P. W., Hoskins R. A., Galle R. F. The genome sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185–2195. doi: 10.1126/science.287.5461.2185. [DOI] [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  3. Anderson S., Bankier A. T., Barrell B. G., de Bruijn M. H., Coulson A. R., Drouin J., Eperon I. C., Nierlich D. P., Roe B. A., Sanger F. Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457–465. doi: 10.1038/290457a0. [DOI] [PubMed] [Google Scholar]
  4. Arnaudo E., Hirano M., Seelan R. S., Milatovich A., Hsieh C. L., Fabrizi G. M., Grossman L. I., Francke U., Schon E. A. Tissue-specific expression and chromosome assignment of genes specifying two isoforms of subunit VIIa of human cytochrome c oxidase. Gene. 1992 Oct 1;119(2):299–305. doi: 10.1016/0378-1119(92)90287-y. [DOI] [PubMed] [Google Scholar]
  5. Caggese C., Ragone G., Perrini B., Moschetti R., De Pinto V., Caizzi R., Barsanti P. Identification of nuclear genes encoding mitochondrial proteins: isolation of a collection of D. melanogaster cDNAs homologous to sequences in the Human Gene Index database. Mol Gen Genet. 1999 Feb;261(1):64–70. doi: 10.1007/s004380050942. [DOI] [PubMed] [Google Scholar]
  6. Capaldi R. A. Structure and function of cytochrome c oxidase. Annu Rev Biochem. 1990;59:569–596. doi: 10.1146/annurev.bi.59.070190.003033. [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. Chou T. B., Noll E., Perrimon N. Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras. Development. 1993 Dec;119(4):1359–1369. doi: 10.1242/dev.119.4.1359. [DOI] [PubMed] [Google Scholar]
  9. 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. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fabrizi G. M., Rizzuto R., Nakase H., Mita S., Kadenbach B., Schon E. A. Sequence of a cDNA specifying subunit VIa of human cytochrome c oxidase. Nucleic Acids Res. 1989 Aug 11;17(15):6409–6409. doi: 10.1093/nar/17.15.6409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Frolov M. V., Benevolenskaya E. V., Birchler J. A. The oxen gene of Drosophila encodes a homolog of subunit 9 of yeast ubiquinol-cytochrome c oxidoreductase complex: evidence for modulation of gene expression in response to mitochondrial activity. Genetics. 2000 Dec;156(4):1727–1736. doi: 10.1093/genetics/156.4.1727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. George H., Terracol R. The vrille gene of Drosophila is a maternal enhancer of decapentaplegic and encodes a new member of the bZIP family of transcription factors. Genetics. 1997 Aug;146(4):1345–1363. doi: 10.1093/genetics/146.4.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Golic K. G., Lindquist S. The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell. 1989 Nov 3;59(3):499–509. doi: 10.1016/0092-8674(89)90033-0. [DOI] [PubMed] [Google Scholar]
  14. Hartenstein K., Sinha P., Mishra A., Schenkel H., Török I., Mechler B. M. The congested-like tracheae gene of Drosophila melanogaster encodes a member of the mitochondrial carrier family required for gas-filling of the tracheal system and expansion of the wings after eclosion. Genetics. 1997 Dec;147(4):1755–1768. doi: 10.1093/genetics/147.4.1755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hayward D. C., Delaney S. J., Campbell H. D., Ghysen A., Benzer S., Kasprzak A. B., Cotsell J. N., Young I. G., Miklos G. L. The sluggish-A gene of Drosophila melanogaster is expressed in the nervous system and encodes proline oxidase, a mitochondrial enzyme involved in glutamate biosynthesis. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2979–2983. doi: 10.1073/pnas.90.7.2979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Iyengar B., Roote J., Campos A. R. The tamas gene, identified as a mutation that disrupts larval behavior in Drosophila melanogaster, codes for the mitochondrial DNA polymerase catalytic subunit (DNApol-gamma125). Genetics. 1999 Dec;153(4):1809–1824. doi: 10.1093/genetics/153.4.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jacobs H., Stratmann R., Lehner C. A screen for lethal mutations in the chromosomal region 59AB suggests that bellwether encodes the alpha subunit of the mitochondrial ATP synthase in Drosophila melanogaster. Mol Gen Genet. 1998 Sep;259(4):383–387. doi: 10.1007/s004380050826. [DOI] [PubMed] [Google Scholar]
  18. Jin Y. S., Anderson K. V. Dominant and recessive alleles of the Drosophila easter gene are point mutations at conserved sites in the serine protease catalytic domain. Cell. 1990 Mar 9;60(5):873–881. doi: 10.1016/0092-8674(90)90100-s. [DOI] [PubMed] [Google Scholar]
  19. Kadenbach B., Merle P. On the function of multiple subunits of cytochrome c oxidase from higher eukaryotes. FEBS Lett. 1981 Nov 30;135(1):1–11. doi: 10.1016/0014-5793(81)80932-5. [DOI] [PubMed] [Google Scholar]
  20. Koga Y., Fabrizi G. M., Mita S., Arnaudo E., Lomax M. I., Aqua M. S., Grossman L. I., Schon E. A. Sequence of a cDNA specifying subunit VIIc of human cytochrome c oxidase. Nucleic Acids Res. 1990 Feb 11;18(3):684–684. doi: 10.1093/nar/18.3.684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kurzik-Dumke U., Debes A., Kaymer M., Dienes P. Mitochondrial localization and temporal expression of the Drosophila melanogaster DnaJ homologous tumor suppressor Tid50. Cell Stress Chaperones. 1998 Mar;3(1):12–27. doi: 10.1379/1466-1268(1998)003<0012:mlateo>2.3.co;2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kurzik-Dumke U., Phannavong B., Gundacker D., Gateff E. Genetic, cytogenetic and developmental analysis of the Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal discs (1(2)tid). Differentiation. 1992 Oct;51(2):91–104. doi: 10.1111/j.1432-0436.1992.tb00685.x. [DOI] [PubMed] [Google Scholar]
  23. Lenka N., Vijayasarathy C., Mullick J., Avadhani N. G. Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex. Prog Nucleic Acid Res Mol Biol. 1998;61:309–344. doi: 10.1016/s0079-6603(08)60830-2. [DOI] [PubMed] [Google Scholar]
  24. Leonard J. V., Schapira A. H. Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet. 2000 Jan 29;355(9201):389–394. doi: 10.1016/s0140-6736(99)05226-5. [DOI] [PubMed] [Google Scholar]
  25. Morisato D., Anderson K. V. Signaling pathways that establish the dorsal-ventral pattern of the Drosophila embryo. Annu Rev Genet. 1995;29:371–399. doi: 10.1146/annurev.ge.29.120195.002103. [DOI] [PubMed] [Google Scholar]
  26. O'Hare K., Rubin G. M. Structures of P transposable elements and their sites of insertion and excision in the Drosophila melanogaster genome. Cell. 1983 Aug;34(1):25–35. doi: 10.1016/0092-8674(83)90133-2. [DOI] [PubMed] [Google Scholar]
  27. Otsuka M., Mizuno Y., Yoshida M., Kagawa Y., Ohta S. Nucleotide sequence of cDNA encoding human cytochrome c oxidase subunit VIc. Nucleic Acids Res. 1988 Nov 25;16(22):10916–10916. doi: 10.1093/nar/16.22.10916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Parikh V. S., Morgan M. M., Scott R., Clements L. S., Butow R. A. The mitochondrial genotype can influence nuclear gene expression in yeast. Science. 1987 Jan 30;235(4788):576–580. doi: 10.1126/science.3027892. [DOI] [PubMed] [Google Scholar]
  29. Poyton R. O. Assembling a time bomb--cytochrome c oxidase and disease. Nat Genet. 1998 Dec;20(4):316–317. doi: 10.1038/3778. [DOI] [PubMed] [Google Scholar]
  30. Poyton R. O., McEwen J. E. Crosstalk between nuclear and mitochondrial genomes. Annu Rev Biochem. 1996;65:563–607. doi: 10.1146/annurev.bi.65.070196.003023. [DOI] [PubMed] [Google Scholar]
  31. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  32. Rizzuto R., Nakase H., Zeviani M., DiMauro S., Schon E. A. Subunit Va of human and bovine cytochrome c oxidase is highly conserved. Gene. 1988 Sep 30;69(2):245–256. doi: 10.1016/0378-1119(88)90435-0. [DOI] [PubMed] [Google Scholar]
  33. Robertson H. M., Preston C. R., Phillis R. W., Johnson-Schlitz D. M., Benz W. K., Engels W. R. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics. 1988 Mar;118(3):461–470. doi: 10.1093/genetics/118.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Roth S., Hiromi Y., Godt D., Nüsslein-Volhard C. cactus, a maternal gene required for proper formation of the dorsoventral morphogen gradient in Drosophila embryos. Development. 1991 Jun;112(2):371–388. doi: 10.1242/dev.112.2.371. [DOI] [PubMed] [Google Scholar]
  35. Royden C. S., Pirrotta V., Jan L. Y. The tko locus, site of a behavioral mutation in D. melanogaster, codes for a protein homologous to prokaryotic ribosomal protein S12. Cell. 1987 Oct 23;51(2):165–173. doi: 10.1016/0092-8674(87)90144-9. [DOI] [PubMed] [Google Scholar]
  36. Rubin G. M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M., Harvey D. A. A Drosophila complementary DNA resource. Science. 2000 Mar 24;287(5461):2222–2224. doi: 10.1126/science.287.5461.2222. [DOI] [PubMed] [Google Scholar]
  37. Sadlock J. E., Lightowlers R. N., Capaldi R. A., Schon E. A. Isolation of a cDNA specifying subunit VIIb of human cytochrome c oxidase. Biochim Biophys Acta. 1993 Feb 20;1172(1-2):223–225. doi: 10.1016/0167-4781(93)90301-s. [DOI] [PubMed] [Google Scholar]
  38. Sato J. D., Powell D. J., Roberts D. B. Purification of the mRNAs encoding the subunits of larval serum proteins 1 and 2 of Drosophila melanogaster. Eur J Biochem. 1982 Nov;128(1):199–207. doi: 10.1111/j.1432-1033.1982.tb06952.x. [DOI] [PubMed] [Google Scholar]
  39. Spencer F. A., Hoffmann F. M., Gelbart W. M. Decapentaplegic: a gene complex affecting morphogenesis in Drosophila melanogaster. Cell. 1982 Mar;28(3):451–461. doi: 10.1016/0092-8674(82)90199-4. [DOI] [PubMed] [Google Scholar]
  40. Spradling A. C., Stern D. M., Kiss I., Roote J., Laverty T., Rubin G. M. Gene disruptions using P transposable elements: an integral component of the Drosophila genome project. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10824–10830. doi: 10.1073/pnas.92.24.10824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Spradling A. C., Stern D., Beaton A., Rhem E. J., Laverty T., Mozden N., Misra S., Rubin G. M. The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes. Genetics. 1999 Sep;153(1):135–177. doi: 10.1093/genetics/153.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Stowers R. S., Schwarz T. L. A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype. Genetics. 1999 Aug;152(4):1631–1639. doi: 10.1093/genetics/152.4.1631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Suske G., Enders C., Schlerf A., Kadenbach B. Organization and nucleotide sequence of two chromosomal genes for rat cytochrome c oxidase subunit VIc: a structural and a processed gene. DNA. 1988 Apr;7(3):163–171. doi: 10.1089/dna.1988.7.163. [DOI] [PubMed] [Google Scholar]
  44. Taanman J. W., Schrage C., Ponne N., Bolhuis P., de Vries H., Agsteribbe E. Nucleotide sequence of cDNA encoding subunit VIb of human cytochrome c oxidase. Nucleic Acids Res. 1989 Feb 25;17(4):1766–1766. doi: 10.1093/nar/17.4.1766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. Wright R. M., Dircks L. K., Poyton R. O. Characterization of COX9, the nuclear gene encoding the yeast mitochondrial protein cytochrome c oxidase subunit VIIa. Subunit VIIa lacks a leader peptide and is an essential component of the holoenzyme. J Biol Chem. 1986 Dec 25;261(36):17183–17191. [PubMed] [Google Scholar]
  47. Xu T., Rubin G. M. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development. 1993 Apr;117(4):1223–1237. doi: 10.1242/dev.117.4.1223. [DOI] [PubMed] [Google Scholar]
  48. Zeviani M., Nakagawa M., Herbert J., Lomax M. I., Grossman L. I., Sherbany A. A., Miranda A. F., DiMauro S., Schon E. A. Isolation of a cDNA clone encoding subunit IV of human cytochrome c oxidase. Gene. 1987;55(2-3):205–217. doi: 10.1016/0378-1119(87)90281-2. [DOI] [PubMed] [Google Scholar]
  49. Zeviani M., Sakoda S., Sherbany A. A., Nakase H., Rizzuto R., Samitt C. E., DiMauro S., Schon E. A. Sequence of cDNAs encoding subunit Vb of human and bovine cytochrome c oxidase. Gene. 1988 May 15;65(1):1–11. doi: 10.1016/0378-1119(88)90411-8. [DOI] [PubMed] [Google Scholar]
  50. Zhang Y. Q., Roote J., Brogna S., Davis A. W., Barbash D. A., Nash D., Ashburner M. stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster. Genetics. 1999 Oct;153(2):891–903. doi: 10.1093/genetics/153.2.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. de Bruijn M. H. Drosophila melanogaster mitochondrial DNA, a novel organization and genetic code. Nature. 1983 Jul 21;304(5923):234–241. doi: 10.1038/304234a0. [DOI] [PubMed] [Google Scholar]

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