• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of transbhomepageaboutsubmitalertseditorial board
Philos Trans R Soc Lond B Biol Sci. Nov 29, 2000; 355(1403): 1573–1580.
PMCID: PMC1692889

Do mitochondria recombine in humans?


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.

Full Text

The Full Text of this article is available as a PDF (210K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Arctander P. Mitochondrial recombination? Science. 1999 Jun 25;284(5423):2090–2091. [PubMed]
  • Awadalla P, Charlesworth D. Recombination and selection at Brassica self-incompatibility loci. Genetics. 1999 May;152(1):413–425. [PMC free article] [PubMed]
  • Awadalla P, Eyre-Walker A, Smith JM. Linkage disequilibrium and recombination in hominid mitochondrial DNA. Science. 1999 Dec 24;286(5449):2524–2525. [PubMed]
  • Ballinger SW, Schurr TG, Torroni A, Gan YY, Hodge JA, Hassan K, Chen KH, Wallace DC. Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient mongoloid migrations. Genetics. 1992 Jan;130(1):139–152. [PMC free article] [PubMed]
  • Bidooki SK, Johnson MA, Chrzanowska-Lightowlers Z, Bindoff LA, Lightowlers RN. Intracellular mitochondrial triplasmy in a patient with two heteroplasmic base changes. Am J Hum Genet. 1997 Jun;60(6):1430–1438. [PMC free article] [PubMed]
  • Birky CW., 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. [PMC free article] [PubMed]
  • Cann RL, Stoneking M, Wilson AC. Mitochondrial DNA and human evolution. Nature. 1987 Jan 1;325(6099):31–36. [PubMed]
  • Chen YS, Torroni A, Excoffier L, Santachiara-Benerecetti AS, Wallace DC. 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]
  • Cummins JM, Wakayama T, Yanagimachi R. Fate of microinjected sperm components in the mouse oocyte and embryo. Zygote. 1997 Nov;5(4):301–308. [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Eyre-Walker A, Smith NH, Smith JM. How clonal are human mitochondria? Proc Biol Sci. 1999 Mar 7;266(1418):477–483. [PMC free article] [PubMed]
  • Eyre-Walker A, Smith NH, Smith J Maynard. Reply to Macaulay et al. (1999): mitochondrial DNA recombination-reasons to panic. Proc Biol Sci. 1999 Oct 22;266(1433):2041–2041. [PMC free article]
  • Gill P, Ivanov PL, 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. [PubMed]
  • Gyllensten U, Wharton D, Wilson AC. Maternal inheritance of mitochondrial DNA during backcrossing of two species of mice. J Hered. 1985 Sep-Oct;76(5):321–324. [PubMed]
  • Gyllensten U, Wharton D, Josefsson A, Wilson AC. Paternal inheritance of mitochondrial DNA in mice. Nature. 1991 Jul 18;352(6332):255–257. [PubMed]
  • Hagelberg E, Goldman N, Lió P, Whelan S, Schiefenhövel W, Clegg JB, Bowden DK. Evidence for mitochondrial DNA recombination in a human population of island Melanesia. Proc Biol Sci. 1999 Mar 7;266(1418):485–492. [PMC free article] [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]
  • Hedrick PW. Gametic disequilibrium measures: proceed with caution. Genetics. 1987 Oct;117(2):331–341. [PMC free article] [PubMed]
  • Hoelzel AR. Evolution by DNA turnover in the control region of vertebrate mitochondrial DNA. Curr Opin Genet Dev. 1993 Dec;3(6):891–895. [PubMed]
  • Houshmand M, Holme E, Hanson C, Wennerholm UB, Hamberger L. Is paternal mitochondrial DNA transferred to the offspring following intracytoplasmic sperm injection? J Assist Reprod Genet. 1997 Apr;14(4):223–227. [PMC free article] [PubMed]
  • Howell N, Kubacka I, Mackey DA. How rapidly does the human mitochondrial genome evolve? Am J Hum Genet. 1996 Sep;59(3):501–509. [PMC free article] [PubMed]
  • Hudson RR, Kaplan NL. Statistical properties of the number of recombination events in the history of a sample of DNA sequences. Genetics. 1985 Sep;111(1):147–164. [PMC free article] [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]
  • Jorde LB, Bamshad M. Questioning evidence for recombination in human mitochondrial DNA. Science. 2000 Jun 16;288(5473):1931–1931. [PubMed]
  • Jorde LB, Bamshad M, Rogers AR. Using mitochondrial and nuclear DNA markers to reconstruct human evolution. Bioessays. 1998 Feb;20(2):126–136. [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. [PMC free article] [PubMed]
  • Kondo R, Satta Y, Matsuura ET, Ishiwa H, Takahata N, Chigusa SI. Incomplete maternal transmission of mitochondrial DNA in Drosophila. Genetics. 1990 Nov;126(3):657–663. [PMC free article] [PubMed]
  • 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]
  • Lunt DH, Hyman BC. Animal mitochondrial DNA recombination. Nature. 1997 May 15;387(6630):247–247. [PubMed]
  • Macaulay V, Richards M, Sykes B. Mitochondrial DNA recombination-no need to panic. Proc Biol Sci. 1999 Oct 22;266(1433):2037–2042. [PMC free article] [PubMed]
  • Maynard Smith J, Smith NH. Detecting recombination from gene trees. Mol Biol Evol. 1998 May;15(5):590–599. [PubMed]
  • Smith JM. The detection and measurement of recombination from sequence data. Genetics. 1999 Oct;153(2):1021–1027. [PMC free article] [PubMed]
  • Miyashita N, Langley CH. Molecular and phenotypic variation of the white locus region in Drosophila melanogaster. Genetics. 1988 Sep;120(1):199–212. [PMC free article] [PubMed]
  • Ohno K, Yamamoto M, Engel AG, Harper CM, Roberts LR, Tan GH, Fatourechi V. MELAS- and Kearns-Sayre-type co-mutation [corrected] with myopathy and autoimmune polyendocrinopathy. Ann Neurol. 1996 Jun;39(6):761–766. [PubMed]
  • Parsons TJ, Muniec DS, Sullivan K, Woodyatt N, Alliston-Greiner R, Wilson MR, Berry DL, Holland KA, Weedn VW, Gill P, et al. A high observed substitution rate in the human mitochondrial DNA control region. Nat Genet. 1997 Apr;15(4):363–368. [PubMed]
  • Rawson PD, Secor CL, Hilbish TJ. 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. [PMC free article] [PubMed]
  • Riley MA, Hallas ME, Lewontin RC. Distinguishing the forces controlling genetic variation at the Xdh locus in Drosophila pseudoobscura. Genetics. 1989 Oct;123(2):359–369. [PMC free article] [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]
  • Saville BJ, Kohli Y, Anderson JB. mtDNA recombination in a natural population. Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1331–1335. [PMC free article] [PubMed]
  • Schaeffer SW, Miller EL. 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. [PMC free article] [PubMed]
  • Shitara H, Hayashi JI, 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. [PMC free article] [PubMed]
  • Sigurğardóttir S, Helgason A, Gulcher JR, Stefansson K, Donnelly P. The mutation rate in the human mtDNA control region. Am J Hum Genet. 2000 May;66(5):1599–1609. [PMC free article] [PubMed]
  • Skibinski DO, Gallagher C, Beynon CM. Mitochondrial DNA inheritance. Nature. 1994 Apr 28;368(6474):817–818. [PubMed]
  • Smith LC, Alcivar AA. Cytoplasmic inheritance and its effects on development and performance. J Reprod Fertil Suppl. 1993;48:31–43. [PubMed]
  • Soodyall H, Jenkins T, Mukherjee A, du Toit E, Roberts DF, Stoneking M. The founding mitochondrial DNA lineages of Tristan da Cunha Islanders. Am J Phys Anthropol. 1997 Oct;104(2):157–166. [PubMed]
  • Starikovskaya YB, Sukernik RI, Schurr TG, Kogelnik AM, Wallace DC. 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. [PMC free article] [PubMed]
  • Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G. Ubiquitin tag for sperm mitochondria. Nature. 1999 Nov 25;402(6760):371–372. [PubMed]
  • 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. [PubMed]
  • Thomas DY, Wilkie D. Recombination of mitochondrial drug-resistance factors in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1968 Feb 26;30(4):368–372. [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]
  • Torroni A, Schurr TG, Yang CC, Szathmary EJ, Williams RC, Schanfield MS, Troup GA, Knowler WC, Lawrence DN, Weiss KM, et al. 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. [PMC free article] [PubMed]
  • Torroni A, Sukernik RI, Schurr TG, Starikorskaya YB, Cabell MF, Crawford MH, Comuzzie AG, Wallace DC. 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]
  • Torroni A, Lott MT, Cabell MF, Chen YS, Lavergne L, Wallace DC. 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]
  • Torroni A, Huoponen K, Francalacci P, Petrozzi M, Morelli L, Scozzari R, Obinu D, Savontaus ML, Wallace DC. Classification of European mtDNAs from an analysis of three European populations. Genetics. 1996 Dec;144(4):1835–1850. [PMC free article] [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]
  • 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. [PMC free article] [PubMed]
  • Wolstenholme DR. Animal mitochondrial DNA: structure and evolution. Int Rev Cytol. 1992;141:173–216. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Zouros E, Ball AO, Saavedra C, Freeman KR. Mitochondrial DNA inheritance. Nature. 1994 Apr 28;368(6474):818–818. [PubMed]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...