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. 1992 Dec 1;89(23):11528–11532. doi: 10.1073/pnas.89.23.11528

Stable heteroplasmy for a large-scale deletion in the coding region of Drosophila subobscura mitochondrial DNA.

A Volz-Lingenhöhl 1, M Solignac 1, D Sperlich 1
PMCID: PMC50585  PMID: 1454843

Abstract

Due to the extremely economic organization of the animal mitochondrial genome, large-scale deletions are rarely found in animal mtDNA. We report the occurrence of a massive deletion in the coding region of mtDNA in Drosophila subobscura. Restriction mapping and nucleotide sequence analysis revealed that the deletion encompasses six protein genes and four tRNAs. All individuals of an isofemale strain proved to be heteroplasmic for normal and deficient mtDNA molecules. This type of heteroplasmy resembles one observed in patients with mitochondrial myopathies but differs in that the fitness of heteroplasmic flies is not significantly reduced even though the mutant mtDNA constitutes 50-80% of total mtDNA in most of the individuals studied. The heteroplasmic strain is genetically stable: despite extensive screening not a single homoplasmic fly was observed since the foundation of the line.

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Selected References

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  1. Afonso J. M., Pestano J., Hernández M. Rapid isolation of mitochondrial DNA from Drosophila adults. Biochem Genet. 1988 Jun;26(5-6):381–386. doi: 10.1007/BF02401791. [DOI] [PubMed] [Google Scholar]
  2. Afonso J. M., Volz A., Hernandez M., Ruttkay H., Gonzalez M., Larruga J. M., Cabrera V. M., Sperlich D. Mitochondrial DNA variation and genetic structure in Old-World populations of Drosophila subobscura. Mol Biol Evol. 1990 Mar;7(2):123–142. doi: 10.1093/oxfordjournals.molbev.a040590. [DOI] [PubMed] [Google Scholar]
  3. Bentzen P., Leggett W. C., Brown G. G. Length and restriction site heteroplasmy in the mitochondrial DNA of american shad (alosa sapidissima). Genetics. 1988 Mar;118(3):509–518. doi: 10.1093/genetics/118.3.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bermingham E., Lamb T., Avise J. C. Size polymorphism and heteroplasmy in the mitochondrial DNA of lower vertebrates. J Hered. 1986 Jul-Aug;77(4):249–252. doi: 10.1093/oxfordjournals.jhered.a110230. [DOI] [PubMed] [Google Scholar]
  5. Boursot P., Yonekawa H., Bonhomme F. Heteroplasmy in mice with deletion of a large coding region of mitochondrial DNA. Mol Biol Evol. 1987 Jan;4(1):46–55. doi: 10.1093/oxfordjournals.molbev.a040421. [DOI] [PubMed] [Google Scholar]
  6. Boyce T. M., Zwick M. E., Aquadro C. F. Mitochondrial DNA in the bark weevils: size, structure and heteroplasmy. Genetics. 1989 Dec;123(4):825–836. doi: 10.1093/genetics/123.4.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Buroker N. E., Brown J. R., Gilbert T. A., O'Hara P. J., Beckenbach A. T., Thomas W. K., Smith M. J. Length heteroplasmy of sturgeon mitochondrial DNA: an illegitimate elongation model. Genetics. 1990 Jan;124(1):157–163. doi: 10.1093/genetics/124.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clary D. O., Wolstenholme D. R. The mitochondrial DNA molecular of Drosophila yakuba: nucleotide sequence, gene organization, and genetic code. J Mol Evol. 1985;22(3):252–271. doi: 10.1007/BF02099755. [DOI] [PubMed] [Google Scholar]
  9. Cornuet J. M., Garnery L., Solignac M. Putative origin and function of the intergenic region between COI and COII of Apis mellifera L. mitochondrial DNA. Genetics. 1991 Jun;128(2):393–403. doi: 10.1093/genetics/128.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Degoul F., Nelson I., Amselem S., Romero N., Obermaier-Kusser B., Ponsot G., Marsac C., Lestienne P. Different mechanisms inferred from sequences of human mitochondrial DNA deletions in ocular myopathies. Nucleic Acids Res. 1991 Feb 11;19(3):493–496. doi: 10.1093/nar/19.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Densmore L. D., Wright J. W., Brown W. M. Length variation and heteroplasmy are frequent in mitochondrial DNA from parthenogenetic and bisexual lizards (genus Cnemidophorus). Genetics. 1985 Aug;110(4):689–707. doi: 10.1093/genetics/110.4.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fauron C. M., Wolstenholme D. R. Structural heterogeneity of mitochondrial DNA molecules within the genus Drosophila. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3623–3627. doi: 10.1073/pnas.73.10.3623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goddard J. M., Wolstenholme D. R. Origin and direction of replication in mitochondrial DNA molecules from Drosophila melanogaster. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3886–3890. doi: 10.1073/pnas.75.8.3886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hale L. R., Singh R. S. Extensive variation and heteroplasmy in size of mitochondrial DNA among geographic populations of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8813–8817. doi: 10.1073/pnas.83.22.8813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Harrison R. G., Rand D. M., Wheeler W. C. Mitochondrial DNA size variation within individual crickets. Science. 1985 Jun 21;228(4706):1446–1448. doi: 10.1126/science.228.4706.1446. [DOI] [PubMed] [Google Scholar]
  16. Hayasaka K., Ishida T., Horai S. Heteroplasmy and polymorphism in the major noncoding region of mitochondrial DNA in Japanese monkeys: association with tandemly repeated sequences. Mol Biol Evol. 1991 Jul;8(4):399–415. doi: 10.1093/oxfordjournals.molbev.a040660. [DOI] [PubMed] [Google Scholar]
  17. Hoeh W. R., Blakley K. H., Brown W. M. Heteroplasmy suggests limited biparental inheritance of Mytilus mitochondrial DNA. Science. 1991 Mar 22;251(5000):1488–1490. doi: 10.1126/science.1672472. [DOI] [PubMed] [Google Scholar]
  18. Holt I. J., Harding A. E., Morgan-Hughes J. A. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature. 1988 Feb 25;331(6158):717–719. doi: 10.1038/331717a0. [DOI] [PubMed] [Google Scholar]
  19. Hyman B. C., Slater T. M. Recent appearance and molecular characterization of mitochondrial DNA deletions within a defined nematode pedigree. Genetics. 1990 Apr;124(4):845–853. doi: 10.1093/genetics/124.4.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Koehler C. M., Lindberg G. L., Brown D. R., Beitz D. C., Freeman A. E., Mayfield J. E., Myers A. M. Replacement of bovine mitochondrial DNA by a sequence variant within one generation. Genetics. 1991 Sep;129(1):247–255. doi: 10.1093/genetics/129.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Larsson N. G., Holme E., Kristiansson B., Oldfors A., Tulinius M. Progressive increase of the mutated mitochondrial DNA fraction in Kearns-Sayre syndrome. Pediatr Res. 1990 Aug;28(2):131–136. doi: 10.1203/00006450-199008000-00011. [DOI] [PubMed] [Google Scholar]
  22. Latorre A., Moya A., Ayala F. J. Evolution of mitochondrial DNA in Drosophila subobscura. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8649–8653. doi: 10.1073/pnas.83.22.8649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mita S., Rizzuto R., Moraes C. T., Shanske S., Arnaudo E., Fabrizi G. M., Koga Y., DiMauro S., Schon E. A. Recombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNA. Nucleic Acids Res. 1990 Feb 11;18(3):561–567. doi: 10.1093/nar/18.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Monnerot M., Mounolou J. C., Solignac M. Intra-individual length heterogeneity of Rana esculenta mitochondrial DNA. Biol Cell. 1984;52(3):213–218. doi: 10.1111/j.1768-322x.1985.tb00339.x. [DOI] [PubMed] [Google Scholar]
  25. Moraes C. T., DiMauro S., Zeviani M., Lombes A., Shanske S., Miranda A. F., Nakase H., Bonilla E., Werneck L. C., Servidei S. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med. 1989 May 18;320(20):1293–1299. doi: 10.1056/NEJM198905183202001. [DOI] [PubMed] [Google Scholar]
  26. Moritz C., Brown W. M. Tandem duplication of D-loop and ribosomal RNA sequences in lizard mitochondrial DNA. Science. 1986 Sep 26;233(4771):1425–1427. doi: 10.1126/science.3018925. [DOI] [PubMed] [Google Scholar]
  27. Nelson I., Degoul F., Obermaier-Kusser B., Romero N., Borrone C., Marsac C., Vayssiere J. L., Gerbitz K., Fardeau M., Ponsot G. Mapping of heteroplasmic mitochondrial DNA deletions in Kearns-Sayre syndrome. Nucleic Acids Res. 1989 Oct 25;17(20):8117–8124. doi: 10.1093/nar/17.20.8117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Okimoto R., Macfarlane J. L., Wolstenholme D. R. Evidence for the frequent use of TTG as the translation initiation codon of mitochondrial protein genes in the nematodes, Ascaris suum and Caenorhabditis elegans. Nucleic Acids Res. 1990 Oct 25;18(20):6113–6118. doi: 10.1093/nar/18.20.6113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Preiss A., Hartley D. A., Artavanis-Tsakonas S. The molecular genetics of Enhancer of split, a gene required for embryonic neural development in Drosophila. EMBO J. 1988 Dec 1;7(12):3917–3927. doi: 10.1002/j.1460-2075.1988.tb03278.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sander M., Hsieh T. S. Drosophila topoisomerase II double-strand DNA cleavage: analysis of DNA sequence homology at the cleavage site. Nucleic Acids Res. 1985 Feb 25;13(4):1057–1072. doi: 10.1093/nar/13.4.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schon E. A., Rizzuto R., Moraes C. T., Nakase H., Zeviani M., DiMauro S. A direct repeat is a hotspot for large-scale deletion of human mitochondrial DNA. Science. 1989 Apr 21;244(4902):346–349. doi: 10.1126/science.2711184. [DOI] [PubMed] [Google Scholar]
  32. Snyder M., Fraser A. R., Laroche J., Gartner-Kepkay K. E., Zouros E. Atypical mitochondrial DNA from the deep-sea scallop Placopecten magellanicus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7595–7599. doi: 10.1073/pnas.84.21.7595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Solignac M., Monnerot M., Mounolou J. C. Mitochondrial DNA heteroplasmy in Drosophila mauritiana. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6942–6946. doi: 10.1073/pnas.80.22.6942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tamura K., Aotsuka T., Kitagawa O. Mitochondrial DNA polymorphisms in the two subspecies of Drosophila sulfurigaster: relationship between geographic structure of population and nucleotide diversity. Mol Biol Evol. 1991 Jan;8(1):104–114. doi: 10.1093/oxfordjournals.molbev.a040629. [DOI] [PubMed] [Google Scholar]
  35. Wallace D. C. Mitochondrial DNA mutations and neuromuscular disease. Trends Genet. 1989 Jan;5(1):9–13. doi: 10.1016/0168-9525(89)90005-x. [DOI] [PubMed] [Google Scholar]
  36. Wallis G. P. Mitochondrial DNA insertion polymorphism and germ line heteroplasmy in the Triturus cristatus complex. Heredity (Edinb) 1987 Apr;58(Pt 2):229–238. doi: 10.1038/hdy.1987.37. [DOI] [PubMed] [Google Scholar]
  37. Wilkinson G. S., Chapman A. M. Length and sequence variation in evening bat D-loop mtDNA. Genetics. 1991 Jul;128(3):607–617. doi: 10.1093/genetics/128.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zevering C. E., Moritz C., Heideman A., Sturm R. A. Parallel origins of duplications and the formation of pseudogenes in mitochondrial DNA from parthenogenetic lizards (Heteronotia binoei; Gekkonidae). J Mol Evol. 1991 Nov;33(5):431–441. doi: 10.1007/BF02103135. [DOI] [PubMed] [Google Scholar]

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