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. 2000 Nov 29;355(1403):1573–1580. doi: 10.1098/rstb.2000.0718

Do mitochondria recombine in humans?

A Eyre-Walker 1
PMCID: PMC1692889  PMID: 11127902

Abstract

Until very recently, mitochondria were thought to be clonally inherited through the maternal line in most higher animals. However, three papers published in 2000 claimed population-genetic evidence of recombination in human mitochondrial DNA. Here I review the current state of the debate. I review the evidence for the two main pathways by which recombination might occur: through paternal leakage and via a mitochondrial DNA sequence in the nuclear genome. There is no strong evidence for either pathway, although paternal leakage seems a definite possibility. However, the population-genetic evidence, although not conclusive, is strongly suggestive of recombination in mitochondrial DNA. The implications of non-clonality for our understanding of human and mitochondrial evolution are discussed.

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Selected References

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  1. Arctander P. Mitochondrial recombination? Science. 1999 Jun 25;284(5423):2090–2091. doi: 10.1126/science.284.5423.2089e. [DOI] [PubMed] [Google Scholar]
  2. Awadalla P., Charlesworth D. Recombination and selection at Brassica self-incompatibility loci. Genetics. 1999 May;152(1):413–425. doi: 10.1093/genetics/152.1.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Awadalla P., Eyre-Walker A., Smith J. M. Linkage disequilibrium and recombination in hominid mitochondrial DNA. Science. 1999 Dec 24;286(5449):2524–2525. doi: 10.1126/science.286.5449.2524. [DOI] [PubMed] [Google Scholar]
  4. Ballinger S. W., Schurr T. G., Torroni A., Gan Y. Y., Hodge J. A., Hassan K., Chen K. H., Wallace D. C. Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient mongoloid migrations. Genetics. 1992 Jan;130(1):139–152. doi: 10.1093/genetics/130.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bidooki S. K., Johnson M. A., Chrzanowska-Lightowlers Z., Bindoff L. A., Lightowlers R. N. Intracellular mitochondrial triplasmy in a patient with two heteroplasmic base changes. Am J Hum Genet. 1997 Jun;60(6):1430–1438. doi: 10.1086/515460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Birky C. W., Jr Uniparental inheritance of mitochondrial and chloroplast genes: mechanisms and evolution. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11331–11338. doi: 10.1073/pnas.92.25.11331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cann R. L., Stoneking M., Wilson A. C. Mitochondrial DNA and human evolution. Nature. 1987 Jan 1;325(6099):31–36. doi: 10.1038/325031a0. [DOI] [PubMed] [Google Scholar]
  8. Chen Y. S., Torroni A., Excoffier L., Santachiara-Benerecetti A. S., Wallace D. C. Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups. Am J Hum Genet. 1995 Jul;57(1):133–149. [PMC free article] [PubMed] [Google Scholar]
  9. Cummins J. M., Wakayama T., Yanagimachi R. Fate of microinjected sperm components in the mouse oocyte and embryo. Zygote. 1997 Nov;5(4):301–308. doi: 10.1017/s0967199400003889. [DOI] [PubMed] [Google Scholar]
  10. Danan C., Sternberg D., Van Steirteghem A., Cazeneuve C., Duquesnoy P., Besmond C., Goossens M., Lissens W., Amselem S. Evaluation of parental mitochondrial inheritance in neonates born after intracytoplasmic sperm injection. Am J Hum Genet. 1999 Aug;65(2):463–473. doi: 10.1086/302484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Excoffier L., Yang Z. Substitution rate variation among sites in mitochondrial hypervariable region I of humans and chimpanzees. Mol Biol Evol. 1999 Oct;16(10):1357–1368. doi: 10.1093/oxfordjournals.molbev.a026046. [DOI] [PubMed] [Google Scholar]
  12. Eyre-Walker A., Smith N. H., Smith J. M. How clonal are human mitochondria? Proc Biol Sci. 1999 Mar 7;266(1418):477–483. doi: 10.1098/rspb.1999.0662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gill P., Ivanov P. L., Kimpton C., Piercy R., Benson N., Tully G., Evett I., Hagelberg E., Sullivan K. Identification of the remains of the Romanov family by DNA analysis. Nat Genet. 1994 Feb;6(2):130–135. doi: 10.1038/ng0294-130. [DOI] [PubMed] [Google Scholar]
  14. Gyllensten U., Wharton D., Josefsson A., Wilson A. C. Paternal inheritance of mitochondrial DNA in mice. Nature. 1991 Jul 18;352(6332):255–257. doi: 10.1038/352255a0. [DOI] [PubMed] [Google Scholar]
  15. Gyllensten U., Wharton D., Wilson A. C. Maternal inheritance of mitochondrial DNA during backcrossing of two species of mice. J Hered. 1985 Sep-Oct;76(5):321–324. doi: 10.1093/oxfordjournals.jhered.a110103. [DOI] [PubMed] [Google Scholar]
  16. Hagelberg E., Goldman N., Lió P., Whelan S., Schiefenhövel W., Clegg J. B., Bowden D. K. Evidence for mitochondrial DNA recombination in a human population of island Melanesia. Proc Biol Sci. 1999 Mar 7;266(1418):485–492. doi: 10.1098/rspb.1999.0663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hasegawa M., Di Rienzo A., Kocher T. D., Wilson A. C. Toward a more accurate time scale for the human mitochondrial DNA tree. J Mol Evol. 1993 Oct;37(4):347–354. doi: 10.1007/BF00178865. [DOI] [PubMed] [Google Scholar]
  18. Hedrick P. W. Gametic disequilibrium measures: proceed with caution. Genetics. 1987 Oct;117(2):331–341. doi: 10.1093/genetics/117.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hoelzel A. R. Evolution by DNA turnover in the control region of vertebrate mitochondrial DNA. Curr Opin Genet Dev. 1993 Dec;3(6):891–895. doi: 10.1016/0959-437x(93)90010-m. [DOI] [PubMed] [Google Scholar]
  20. Houshmand M., Holme E., Hanson C., Wennerholm U. B., Hamberger L. Is paternal mitochondrial DNA transferred to the offspring following intracytoplasmic sperm injection? J Assist Reprod Genet. 1997 Apr;14(4):223–227. doi: 10.1007/BF02766114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Howell N., Kubacka I., Mackey D. A. How rapidly does the human mitochondrial genome evolve? Am J Hum Genet. 1996 Sep;59(3):501–509. [PMC free article] [PubMed] [Google Scholar]
  22. Hudson R. R., Kaplan N. L. Statistical properties of the number of recombination events in the history of a sample of DNA sequences. Genetics. 1985 Sep;111(1):147–164. doi: 10.1093/genetics/111.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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. doi: 10.1038/ng0298-109. [DOI] [PubMed] [Google Scholar]
  24. Jorde L. B., Bamshad M. Questioning evidence for recombination in human mitochondrial DNA. Science. 2000 Jun 16;288(5473):1931–1931. [PubMed] [Google Scholar]
  25. Jorde L. B., Bamshad M., Rogers A. R. Using mitochondrial and nuclear DNA markers to reconstruct human evolution. Bioessays. 1998 Feb;20(2):126–136. doi: 10.1002/(SICI)1521-1878(199802)20:2<126::AID-BIES5>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  26. Kaneda H., Hayashi J., Takahama S., Taya C., Lindahl K. F., 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. doi: 10.1073/pnas.92.10.4542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kondo R., Satta Y., Matsuura E. T., Ishiwa H., Takahata N., Chigusa S. I. Incomplete maternal transmission of mitochondrial DNA in Drosophila. Genetics. 1990 Nov;126(3):657–663. doi: 10.1093/genetics/126.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kumar S., Hedrick P., Dowling T., Stoneking M. Questioning evidence for recombination in human mitochondrial DNA. Science. 2000 Jun 16;288(5473):1931–1931. [PubMed] [Google Scholar]
  29. Lunt D. H., Hyman B. C. Animal mitochondrial DNA recombination. Nature. 1997 May 15;387(6630):247–247. doi: 10.1038/387247a0. [DOI] [PubMed] [Google Scholar]
  30. Macaulay V., Richards M., Sykes B. Mitochondrial DNA recombination-no need to panic. Proc Biol Sci. 1999 Oct 22;266(1433):2037–2042. doi: 10.1098/rspb.1999.0883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Maynard Smith J., Smith N. H. Detecting recombination from gene trees. Mol Biol Evol. 1998 May;15(5):590–599. doi: 10.1093/oxfordjournals.molbev.a025960. [DOI] [PubMed] [Google Scholar]
  32. Miyashita N., Langley C. H. Molecular and phenotypic variation of the white locus region in Drosophila melanogaster. Genetics. 1988 Sep;120(1):199–212. doi: 10.1093/genetics/120.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ohno K., Yamamoto M., Engel A. G., Harper C. M., Roberts L. R., Tan G. H., Fatourechi V. MELAS- and Kearns-Sayre-type co-mutation [corrected] with myopathy and autoimmune polyendocrinopathy. Ann Neurol. 1996 Jun;39(6):761–766. doi: 10.1002/ana.410390612. [DOI] [PubMed] [Google Scholar]
  34. doi: 10.1098/rspb.1999.0884. [DOI] [PMC free article] [Google Scholar]
  35. Parsons T. J., Muniec D. S., Sullivan K., Woodyatt N., Alliston-Greiner R., Wilson M. R., Berry D. L., Holland K. A., Weedn V. W., Gill P. A high observed substitution rate in the human mitochondrial DNA control region. Nat Genet. 1997 Apr;15(4):363–368. doi: 10.1038/ng0497-363. [DOI] [PubMed] [Google Scholar]
  36. Rawson P. D., Secor C. L., Hilbish T. J. The effects of natural hybridization on the regulation of doubly uniparental mtDNA inheritance in blue mussels (Mytilus spp.). Genetics. 1996 Sep;144(1):241–248. doi: 10.1093/genetics/144.1.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Riley M. A., Hallas M. E., Lewontin R. C. Distinguishing the forces controlling genetic variation at the Xdh locus in Drosophila pseudoobscura. Genetics. 1989 Oct;123(2):359–369. doi: 10.1093/genetics/123.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rogers A. R., Harpending H. Population growth makes waves in the distribution of pairwise genetic differences. Mol Biol Evol. 1992 May;9(3):552–569. doi: 10.1093/oxfordjournals.molbev.a040727. [DOI] [PubMed] [Google Scholar]
  39. Saville B. J., Kohli Y., Anderson J. B. mtDNA recombination in a natural population. Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1331–1335. doi: 10.1073/pnas.95.3.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schaeffer S. W., Miller E. L. Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region of Drosophila pseudoobscura. Genetics. 1993 Oct;135(2):541–552. doi: 10.1093/genetics/135.2.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Shitara H., Hayashi J. I., Takahama S., Kaneda H., Yonekawa H. Maternal inheritance of mouse mtDNA in interspecific hybrids: segregation of the leaked paternal mtDNA followed by the prevention of subsequent paternal leakage. Genetics. 1998 Feb;148(2):851–857. doi: 10.1093/genetics/148.2.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sigurğardóttir S., Helgason A., Gulcher J. R., Stefansson K., Donnelly P. The mutation rate in the human mtDNA control region. Am J Hum Genet. 2000 Apr 7;66(5):1599–1609. doi: 10.1086/302902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Skibinski D. O., Gallagher C., Beynon C. M. Mitochondrial DNA inheritance. Nature. 1994 Apr 28;368(6474):817–818. doi: 10.1038/368817b0. [DOI] [PubMed] [Google Scholar]
  44. Smith J. M. The detection and measurement of recombination from sequence data. Genetics. 1999 Oct;153(2):1021–1027. doi: 10.1093/genetics/153.2.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Smith L. C., Alcivar A. A. Cytoplasmic inheritance and its effects on development and performance. J Reprod Fertil Suppl. 1993;48:31–43. [PubMed] [Google Scholar]
  46. Soodyall H., Jenkins T., Mukherjee A., du Toit E., Roberts D. F., Stoneking M. The founding mitochondrial DNA lineages of Tristan da Cunha Islanders. Am J Phys Anthropol. 1997 Oct;104(2):157–166. doi: 10.1002/(SICI)1096-8644(199710)104:2<157::AID-AJPA2>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
  47. Starikovskaya Y. B., Sukernik R. I., Schurr T. G., Kogelnik A. M., Wallace D. C. mtDNA diversity in Chukchi and Siberian Eskimos: implications for the genetic history of Ancient Beringia and the peopling of the New World. Am J Hum Genet. 1998 Nov;63(5):1473–1491. doi: 10.1086/302087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sutovsky P., Moreno R. D., Ramalho-Santos J., Dominko T., Simerly C., Schatten G. Ubiquitin tag for sperm mitochondria. Nature. 1999 Nov 25;402(6760):371–372. doi: 10.1038/46466. [DOI] [PubMed] [Google Scholar]
  49. Takai D., Isobe K., Hayashi J. Transcomplementation between different types of respiration-deficient mitochondria with different pathogenic mutant mitochondrial DNAs. J Biol Chem. 1999 Apr 16;274(16):11199–11202. doi: 10.1074/jbc.274.16.11199. [DOI] [PubMed] [Google Scholar]
  50. Thomas D. Y., Wilkie D. Recombination of mitochondrial drug-resistance factors in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1968 Feb 26;30(4):368–372. doi: 10.1016/0006-291x(68)90753-5. [DOI] [PubMed] [Google Scholar]
  51. Thyagarajan B., Padua R. A., Campbell C. Mammalian mitochondria possess homologous DNA recombination activity. J Biol Chem. 1996 Nov 1;271(44):27536–27543. doi: 10.1074/jbc.271.44.27536. [DOI] [PubMed] [Google Scholar]
  52. Torroni A., Huoponen K., Francalacci P., Petrozzi M., Morelli L., Scozzari R., Obinu D., Savontaus M. L., Wallace D. C. Classification of European mtDNAs from an analysis of three European populations. Genetics. 1996 Dec;144(4):1835–1850. doi: 10.1093/genetics/144.4.1835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Torroni A., Lott M. T., Cabell M. F., Chen Y. S., Lavergne L., Wallace D. C. mtDNA and the origin of Caucasians: identification of ancient Caucasian-specific haplogroups, one of which is prone to a recurrent somatic duplication in the D-loop region. Am J Hum Genet. 1994 Oct;55(4):760–776. [PMC free article] [PubMed] [Google Scholar]
  54. Torroni A., Schurr T. G., Yang C. C., Szathmary E. J., Williams R. C., Schanfield M. S., Troup G. A., Knowler W. C., Lawrence D. N., Weiss K. M. Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations. Genetics. 1992 Jan;130(1):153–162. doi: 10.1093/genetics/130.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Torroni A., Sukernik R. I., Schurr T. G., Starikorskaya Y. B., Cabell M. F., Crawford M. H., Comuzzie A. G., Wallace D. C. mtDNA variation of aboriginal Siberians reveals distinct genetic affinities with Native Americans. Am J Hum Genet. 1993 Sep;53(3):591–608. [PMC free article] [PubMed] [Google Scholar]
  56. Vigilant L., Stoneking M., Harpending H., Hawkes K., Wilson A. C. African populations and the evolution of human mitochondrial DNA. Science. 1991 Sep 27;253(5027):1503–1507. doi: 10.1126/science.1840702. [DOI] [PubMed] [Google Scholar]
  57. Wakeley J. Substitution rate variation among sites in hypervariable region 1 of human mitochondrial DNA. J Mol Evol. 1993 Dec;37(6):613–623. doi: 10.1007/BF00182747. [DOI] [PubMed] [Google Scholar]
  58. Wise C. A., 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. doi: 10.1093/genetics/148.1.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Wolstenholme D. R. Animal mitochondrial DNA: structure and evolution. Int Rev Cytol. 1992;141:173–216. doi: 10.1016/s0074-7696(08)62066-5. [DOI] [PubMed] [Google Scholar]
  60. Yoneda M., Miyatake T., Attardi G. Complementation of mutant and wild-type human mitochondrial DNAs coexisting since the mutation event and lack of complementation of DNAs introduced separately into a cell within distinct organelles. Mol Cell Biol. 1994 Apr;14(4):2699–2712. doi: 10.1128/mcb.14.4.2699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Zouros E., Ball A. O., Saavedra C., Freeman K. R. Mitochondrial DNA inheritance. Nature. 1994 Apr 28;368(6474):818–818. doi: 10.1038/368818a0. [DOI] [PubMed] [Google Scholar]

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