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Proc Biol Sci. 1999 March 7; 266(1418): 477–483.
PMCID: PMC1689787

How clonal are human mitochondria?


Phylogenetic trees constructed using human mitochondrial sequences contain a large number of homoplasies. These are due either to repeated mutation or to recombination between mitochondrial lineages. We show that a tree constructed using synonymous variation in the protein coding sequences of 29 largely complete human mitochondrial molecules contains 22 homoplasies at 32 phylogenetically informative sites. This level of homoplasy is very unlikely if inheritance is clonal, even if we take into account base composition bias. There must either be 'hypervariable' sites or recombination between mitochondria. We present evidence which suggests that hypervariable sites do not exist in our data. It therefore seems likely that recombination has occurred between mitochondrial lineages in humans.

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Selected References

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  • Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457–465. [PubMed]
  • Arnason U, Xu X, Gullberg A. Comparison between the complete mitochondrial DNA sequences of Homo and the common chimpanzee based on nonchimeric sequences. J Mol Evol. 1996 Feb;42(2):145–152. [PubMed]
  • Brown MD, Voljavec AS, Lott MT, MacDonald I, Wallace DC. Leber's hereditary optic neuropathy: a model for mitochondrial neurodegenerative diseases. FASEB J. 1992 Jul;6(10):2791–2799. [PubMed]
  • Brown MD, Voljavec AS, Lott MT, Torroni A, Yang CC, Wallace DC. Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy. Genetics. 1992 Jan;130(1):163–173. [PubMed]
  • Bulmer M. Neighboring base effects on substitution rates in pseudogenes. Mol Biol Evol. 1986 Jul;3(4):322–329. [PubMed]
  • Cann RL, Stoneking M, Wilson AC. Mitochondrial DNA and human evolution. Nature. 1987 Jan 1;325(6099):31–36. [PubMed]
  • Coulondre C, Miller JH, Farabaugh PJ, Gilbert W. Molecular basis of base substitution hotspots in Escherichia coli. Nature. 1978 Aug 24;274(5673):775–780. [PubMed]
  • Halliday JA, Glickman BW. Mechanisms of spontaneous mutation in DNA repair-proficient Escherichia coli. Mutat Res. 1991 Sep-Oct;250(1-2):55–71. [PubMed]
  • Hasegawa M, Di Rienzo A, Kocher TD, Wilson AC. Toward a more accurate time scale for the human mitochondrial DNA tree. J Mol Evol. 1993 Oct;37(4):347–354. [PubMed]
  • Jazin E, Soodyall H, Jalonen P, Lindholm E, Stoneking M, Gyllensten U. Mitochondrial mutation rate revisited: hot spots and polymorphism. Nat Genet. 1998 Feb;18(2):109–110. [PubMed]
  • Kaneda H, Hayashi J, Takahama S, Taya C, Lindahl KF, Yonekawa H. Elimination of paternal mitochondrial DNA in intraspecific crosses during early mouse embryogenesis. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4542–4546. [PubMed]
  • Kobayashi Y, Momoi MY, Tominaga K, Shimoizumi H, Nihei K, Yanagisawa M, Kagawa Y, Ohta S. Respiration-deficient cells are caused by a single point mutation in the mitochondrial tRNA-Leu (UUR) gene in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Am J Hum Genet. 1991 Sep;49(3):590–599. [PubMed]
  • Lunt DH, Hyman BC. Animal mitochondrial DNA recombination. Nature. 1997 May 15;387(6630):247–247. [PubMed]
  • Marzuki S, Noer AS, Lertrit P, Thyagarajan D, Kapsa R, Utthanaphol P, Byrne E. Normal variants of human mitochondrial DNA and translation products: the building of a reference data base. Hum Genet. 1991 Dec;88(2):139–145. [PubMed]
  • Maynard Smith J, Smith NH. Detecting recombination from gene trees. Mol Biol Evol. 1998 May;15(5):590–599. [PubMed]
  • Ozawa T, Tanaka M, Sugiyama S, Ino H, Ohno K, Hattori K, Ohbayashi T, Ito T, Deguchi H, Kawamura K, et al. Patients with idiopathic cardiomyopathy belong to the same mitochondrial DNA gene family of Parkinson's disease and mitochondrial encephalomyopathy. Biochem Biophys Res Commun. 1991 May 31;177(1):518–525. [PubMed]
  • Perna NT, Kocher TD. Patterns of nucleotide composition at fourfold degenerate sites of animal mitochondrial genomes. J Mol Evol. 1995 Sep;41(3):353–358. [PubMed]
  • Rogers AR, Harpending H. Population growth makes waves in the distribution of pairwise genetic differences. Mol Biol Evol. 1992 May;9(3):552–569. [PubMed]
  • Sbisà E, Tanzariello F, Reyes A, Pesole G, Saccone C. Mammalian mitochondrial D-loop region structural analysis: identification of new conserved sequences and their functional and evolutionary implications. Gene. 1997 Dec 31;205(1-2):125–140. [PubMed]
  • Thyagarajan B, Padua RA, Campbell C. Mammalian mitochondria possess homologous DNA recombination activity. J Biol Chem. 1996 Nov 1;271(44):27536–27543. [PubMed]
  • Vigilant L, Stoneking M, Harpending H, Hawkes K, Wilson AC. African populations and the evolution of human mitochondrial DNA. Science. 1991 Sep 27;253(5027):1503–1507. [PubMed]
  • Wakeley J. Substitution rate variation among sites in hypervariable region 1 of human mitochondrial DNA. J Mol Evol. 1993 Dec;37(6):613–623. [PubMed]
  • Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ, 2nd, Nikoskelainen EK. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988 Dec 9;242(4884):1427–1430. [PubMed]
  • Wise CA, Sraml M, Easteal S. Departure from neutrality at the mitochondrial NADH dehydrogenase subunit 2 gene in humans, but not in chimpanzees. Genetics. 1998 Jan;148(1):409–421. [PubMed]
  • Yoneda M, Tanno Y, Horai S, Ozawa T, Miyatake T, Tsuji S. A common mitochondrial DNA mutation in the t-RNA(Lys) of patients with myoclonus epilepsy associated with ragged-red fibers. Biochem Int. 1990 Aug;21(5):789–796. [PubMed]

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