Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes

Key Points

  • Genome sequences show extensive tracts of mitochondrial and plastid DNA that are integrated in nuclear chromosomes. Evidence indicates that an active process of DNA translocation from organelles to the nucleus has been ongoing since the origin or organelles from free-living prokaryotes.

  • Movement of DNA from organelles to the nucleus occurs at very high rates. These rates have been measured experimentally for mitochondria in yeast and more recently for plastids using transgenic chloroplast technology in tobacco.

  • Phylogenetic analyses and genome comparisons show that influx of organellar DNA to the nucleus has had a marked quantitative impact on the gene content of eukaryotic chromosomes.

  • Translocated genes might be expressed to provide products that are targeted to all parts of the cell; there is no magic homing device that targets the products of transferred genes back to the organelle of their origin.

  • When a relocated gene becomes expressed as a product that provides a selectable advantage, the original, now duplicate copy (be it mitochondrial, plastid or nuclear) can undergo recombination, mutational decay or deletion.

  • Complete organelle genomes are cropping up in eukaryotic chromosomes, so why are any genes left in organelles at all? The two competing theories that stand in the foreground of this hotly debated issue (redox regulation and hydrophobicity) are contrasted.

  • Observations from genomes and from experimental transfers favour the view that bulk DNA from lysed organelles is the vector that is responsible for gene relocation, although in some groups of eukaryotes, RNA intermediates have been suggested to act as vectors as well.

  • DNA movement between genetic compartments has consequences for strategies of genetic manipulation that aim to sequester transgenes in organelles.

  • The downpour of organelle DNA into eukaryotic chromosomes is an unavoidable consequence of endosymbiosis. This mechanism of natural variation is unique to eukaryotic cells and was an important force in the genesis of eukaryotic genomes.

  • The impact of endosymbiotic gene transfer on eukaryotic chromosomes was probably greatest in the early phases of organelle origins, before the protein import machinery of mitochondria and chloroplasts had been invented.

Abstract

Genome sequences reveal that a deluge of DNA from organelles has constantly been bombarding the nucleus since the origin of organelles. Recent experiments have shown that DNA is transferred from organelles to the nucleus at frequencies that were previously unimaginable. Endosymbiotic gene transfer is a ubiquitous, continuing and natural process that pervades nuclear DNA dynamics. This relentless influx of organelle DNA has abolished organelle autonomy and increased nuclear complexity.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Organellar DNA mobility and the genetic control of biogenesis of mitochondria and chloroplasts.
Figure 2: Reduction of the chloroplast genome over time.

Similar content being viewed by others

References

  1. Baur, E. Das Wesen und die Erblichkeitsverhältnisse der 'Varietates albomarginatae hort' von Pelargonium zonale. Z. Vererbungsl. 1, 330–351 (1909).

    Google Scholar 

  2. Mereschkowsky, C. Über Natur und Ursprung der Chromatophoren im Pflanzenreiche. Biol. Centralbl. 25, 593–604 (1905). [English translation Eur. J. Phycol. 34, 287–295, 1999]. The starting point of endosymbiotic theory. Outlines the reasoning that we still use today to explain the origin of plastids from cyanobacteria, a paper that was many decades ahead of its time.

    Google Scholar 

  3. Margulis, L. Origin of Eukaryotic Cells 349 (Yale Univ. Press, New Haven, 1970). The rediscovery of endosymbiotic theory after Wilson's 1928 condemnation of symbiosis as an evolutionary mechanism (see also reference 2).

    Google Scholar 

  4. Gray, M. W. & Doolittle, W. F. Has the endosymbiont hypothesis been proven? Microbol. Rev. 46, 1–42 (1982).

    CAS  Google Scholar 

  5. Bogorad, L. Evolution of organelles and eukaryotic genomes. Science 188, 891–898 (1975).

    Article  CAS  PubMed  Google Scholar 

  6. Ellis, R. J. Chloroplast proteins: synthesis, transport and assembly. Ann. Rev. Pl. Physiol. 32, 111–137 (1981).

    Article  CAS  Google Scholar 

  7. Weeden, N. F. Genetic and biochemical implications of the endosymbiotic origin of the chloroplast. J. Mol. Evol. 17, 133–139 (1981).

    Article  CAS  PubMed  Google Scholar 

  8. Martin, W. & Herrmann, R. G. Gene transfer from organelles to the nucleus: how much, what happens, and why? Plant Physiol. 118, 9–17 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Simpson, C. L. & Stern, D. B. The treasure trove of algal chloroplast genomes. Surprises in architecture and gene content, and their functional implications. Plant Physiol. 129, 957–966 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gray, M. W., Burger, G. & Lang, B. F. Mitochondrial evolution. Science 283, 1476–1481 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Lang, B. F., Gray, M. W. & Burger, G. Mitochondrial genome evolution and the origin of eukaryotes. Annu. Rev. Genet. 33, 351–397 (1999).

    Article  CAS  PubMed  Google Scholar 

  12. Burger, G., Forget, L., Zhu, Y., Gray, M. W. & Lang, B. F. Unique mitochondrial genome architecture in unicellular relatives of animals. Proc. Natl Acad. Sci. USA 100, 892–897 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Embley, T. M. et al. Hydrogenosomes, mitochondria and early eukaryotic evolution. IUBMB Life 55, 387–395 (2003). An incisive and up-to-date review that covers the biology and evolutionary significance of hydrogenosomes, the mitochondria that endosymbiotic theory nearly forgot.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang, Z., Green, B. R. & Cavalier-Smith, T. Single gene circles in dinoflagellate chloroplast genomes. Nature 400, 155–159 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Hannaert, V. et al. Plant-like traits associated with metabolism of Trypanosoma parasites. Proc. Natl Acad. Sci. USA 100, 1067–1071 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cavalier-Smith, T. Membrane heredity and early chloroplast evolution. Trends Plant Sci. 5, 174–182 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Tielens, A. G., Rotte, C., van Hellemond, J. J. & Martin, W. Mitochondria as we don't know them. Trends Biochem. Sci. 27, 564–572 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Tovar, J. et al. Mitochondrial remnant organelles of Giardia function in iron-sulphur protein maturation. Nature 426, 172–176 (2003).

    Article  CAS  PubMed  Google Scholar 

  19. Martin, W. et al. Evolutionary analysis of Arabidopsis, cyanobacterial, and chloroplast genomes reveals plastid phylogeny and thousands of cyanobacterial genes in the nucleus. Proc. Natl Acad. Sci. USA 99, 12246–12251 (2002). Shows that approximately 18% of the nuclear genes in Arabidopsis come from the ancestral plastid genome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wu, M. et al. The genome sequence and evolution of the reproductive parasite Wolbachia pipientis wMel: a streamlined α-proteobacterium massively infected with mobile genetic elements. PLoS Biology (in the press). Incisive evolutionary insights into endosymbiont genome biology with a genome phylogeny for mitochondrial origin.

  21. Stern, D. B. & Lonsdale, D. M. Mitochondrial and chloroplast genomes of maize have a 12-kilobase DNA sequence in common. Nature 299, 698–702 (1982). The paper that initiated progress; showed that DNA was able to migrate between the genetic compartments of eukaryotes.

    Article  CAS  PubMed  Google Scholar 

  22. Jacobs, H. T. et al. Mitochondrial DNA sequences in the nuclear genome of Strongylocentrotus purpuratus. J. Mol. Biol. 165, 609–632 (1983).

    Article  CAS  PubMed  Google Scholar 

  23. Farrely, F. & Butow, R. A. Rearranged mitochondrial genes in the yeast nuclear genome. Nature 301, 296–301 (1983).

    Article  Google Scholar 

  24. Timmis, J. N. & Scott, N. S. Spinach nuclear and chloroplast DNAs have homologous sequences. Nature 305, 65–67 (1983).

    Article  CAS  Google Scholar 

  25. Ellis, R. J. Promiscuous DNA — chloroplast genes inside plant mitochondria. Nature 299, 678–679 (1982).

    Article  CAS  PubMed  Google Scholar 

  26. Lopez, J. V., Yuhki, N., Masuda, R., Modi, W. & O'Brien, S. J. Numt, a recent transfer and tandem amplification of mitochondrial DNA to the nuclear genome of the domestic cat. J. Mol. Evol. 39, 174–190 (1994).

    CAS  PubMed  Google Scholar 

  27. Bensasson, D., Zhang, D. X. & Hewitt, G. M. Frequent assimilation of mitochondrial DNA by grasshopper nuclear genomes. Mol. Biol. Evol. 17, 406–415 (2000).

    Article  CAS  PubMed  Google Scholar 

  28. Mundy, N. I., Pissinatti, A. & Woodruff, D. S. Multiple nuclear insertions of mitochondrial cytochrome b sequences in callitrichine primates. Mol. Biol. Evol. 17, 1075–1080 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Lu, X. M., Fu, Y. X. & Zhang, Y. P. Evolution of mitochondrial cytochrome b pseudogene in genus Nycticebus. Mol. Biol. Evol. 19, 2337–2341 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. Williams, S. T. & Knowlton, N. Mitochondrial pseudogenes are pervasive and often insidious in the snapping shrimp genus Alpheus. Mol. Biol. Evol. 18, 1484–1493 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Olson, L. E. & Yoder, A. D. Using secondary structure to identify ribosomal numts: cautionary examples from the human genome. Mol. Biol. Evol. 19, 93–100 (2002). Together with reference 32, points out that numts are often mistaken for genuine mitochondrial DNA sequences.

    Article  CAS  PubMed  Google Scholar 

  32. Bensasson, D., Zhang, D., Hartl, D. L. & Hewitt, G. M. Mitochondrial pseudogenes: evolution's misplaced witnesses. Trends Ecol. Evol. 16, 314–321 (2001).

    Article  CAS  PubMed  Google Scholar 

  33. Ricchetti, M., Fairhead, C. & Dujon, B. Mitochondrial DNA repairs double strand breaks in yeast chromosomes. Nature 402, 96–100 (1999). The initial genome-wide survey for numts; indicates a role for recombination in numt integration.

    Article  CAS  PubMed  Google Scholar 

  34. Mourier, T., Hansen, A. J., Willerslev, E. & Arctander, P. The human genome project reveals a continuous transfer of large mitochondrial fragments to the nucleus. Mol. Biol. Evol. 18, 1833–1837 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Tourmen, Y. et al. Structure and chromosomal distribution of human mitochondrial pseudogenes. Genomics 80, 71–77 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Hazkani-Covo, E., Sorek, R. & Graur, D. Evolutionary dynamics of large numts in the human genome: rarity of independent insertions and abundance of post-insertion duplications. J. Mol. Evol. 56, 169–174 (2003). A careful and detailed inspection of numt duplication dynamics during human and primate genome evolution.

    Article  CAS  PubMed  Google Scholar 

  37. Woischnik, M. & Moraes, C. T. Pattern of organisation of human mitochondrial pseudogenes in the nuclear genome. Genome Res. 12, 885–893 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Richly, E. & Leister, D. Numts in sequenced eukaryotic genomes. Mol. Biol. Evol. (in the press).

  39. Lin, X. Y. et al. Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana. Nature 402, 761–768 (1999). Reports a nearly complete, 270-kb copy of the 367-kb Arabidopsis mtDNA near the centromere.

    Article  CAS  PubMed  Google Scholar 

  40. Stupar, R. M. et al. Complex mtDNA constitutes an approximate 620-kb insertion on Arabidopsis thaliana chromosome 2: implication of potential sequencing errors caused by large-unit repeats. Proc. Natl Acad. Sci. USA 98, 5099–5103 (2001). Shows that the 270-kb copy in reference 39 is really the complete 367-kb circle.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. The, Arabidopsis Genome Initiative. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796–815 (2000).

  42. Yuan, Q. et al. Genome sequencing of 239-kb region of rice chromosome 10L reveals a high frequency of gene duplication and a large chloroplast DNA insertion. Mol. Genet. Genom. 267, 713–720 (2002). First hints from genome sequences of large cpDNA chunks (>30 kb) that are integrated in nuclear chromosomes.

    Article  CAS  Google Scholar 

  43. The Rice Chromosome 10 Sequencing Consortium. In-depth view of structure, activity, and evolution of rice chromosome 10. Science 300, 1566–1569 (2003). Reports a nearly complete cpDNA genome chunk (130 kb) that is integrated in the nuclear chromosome.

  44. Shahmuradov, I. A., Akbarova, Y. Y., Solovyev, V. V. & Aliyev, J. A. Abundance of plastid DNA insertions in nuclear genomes of rice and Arabidopsis. Plant Mol. Biol. 52, 923–934 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Ayliffe, M. A. & Timmis, J. N. Tobacco nuclear DNA contains long tracts of homology to chloroplast DNA. Theor. Appl. Genet. 85, 229–238 (1992).

    Article  CAS  PubMed  Google Scholar 

  46. Ayliffe, M. A. & Timmis, J. N. Plastid DNA sequence homologies in the tobacco nuclear genome. Mol. Gen. Genet. 236, 105–112 (1992).

    CAS  PubMed  Google Scholar 

  47. Boore, J. L. Animal mitochondrial genomes. Nucleic Acids Res. 27, 1767–1780 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Brennicke, A., Grohmann, L., Hiesel, R., Knoop, V. & Schuster, W. The mitochondrial genome on its way to the nucleus: different stages of gene transfer in higher plants. FEBS Lett. 325, 140–145 (1993).

    Article  CAS  PubMed  Google Scholar 

  49. Adams, K. L. & Palmer, J. D. Evolution of mitochondrial gene content: gene loss and transfer to the nucleus. Mol. Phylog. Evol. 29, 380–395 (2003). A lucid review of flowering plant mitochondrial gene migration to the nucleus.

    Article  CAS  Google Scholar 

  50. Adams, K. L., Daley, D. O., Qiu, Y. L., Whelan, J. & Palmer, J. D. Repeated, recent and diverse transfers of a mitochondrial gene to the nucleus in flowering plants. Nature 408, 354–357 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Adams, K. L, Qiu Y. -L., Stoutemyer, M. & Palmer J. D. Punctuated evolution of mitochondrial gene content: high and variable rates of mitochondrial gene loss and transfer to the nucleus during angiosperm evolution. Proc. Natl Acad. Sci. USA 99, 9905–9912 (2002). A broad survey of mitochondrial genome reduction that is accompanied by nuclear integration events in flowering plant evolution.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Henze, K. & Martin, W. How are mitochondrial genes transferred to the nucleus? Trends Genet. 17, 383–387 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Thorsness, P. E. & Weber, E. R. Escape and migration of nucleic acids between chloroplasts, mitochondria, and the nucleus. Int. Rev. Cytol. 165, 207–234 (1996). An excellent review that covers the mechanics of gene transfer from organelles to the nucleus in the pre-genome era.

    Article  CAS  PubMed  Google Scholar 

  54. Blanchard, J. L. & Lynch, M. Organellar genes — why do they end up in the nucleus? Trends Genet. 16, 315–320 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Figueroa, P., Gomez, I., Holuigue, L., Araya, A. & Jordana, X. Transfer of rps14 from the mitochondrion to the nucleus in maize implied integration within a gene encoding the iron-sulphur subunit of succinate dehydrogenase and expression by alternative splicing. Plant J. 18, 601–609 (1999). Fortuitous recombination in the establishment of active gene transfers.

    Article  CAS  PubMed  Google Scholar 

  56. Kubo, N., Harada, K., Hirai, A. & Kadowaki, K. A single nuclear transcript encoding mitochondrial RPS14 and SSDHB of rice is processed by alternative splicing: common use of the same mitochondrial targeting signal for different proteins. Proc. Natl Acad. Sci. USA 96, 9207–9211 (1999). The establishment of active gene transfers can involve the recruitment of pre-existing transit peptide regions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Long, M., de Souza, S. J., Rosenberg, C. & Gilbert, W. Exon shuffling and the origin of the mitochondrial targeting function in plant cytochrome c1 precursor. Proc. Natl Acad. Sci. USA 93, 7727–7731 (1996). Gene transfers can involve conversion of a pre-existing nuclear coding region for a cytosolic enzyme into a transit peptide.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Millen, R. S. et al. Many parallel losses of infA from chloroplast DNA during angiosperm evolution with multiple independent transfers to the nucleus. Plant Cell 13, 645–658 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Martin, W. et al. Gene transfer to the nucleus and the evolution of chloroplasts. Nature 393, 162–165 (1998).

    Article  CAS  PubMed  Google Scholar 

  60. Lang, B. F. et al. An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. Nature 387, 493–497 (1997). The still unsurpassed mitchondrial genome in terms of gene content and streamlined organization.

    Article  CAS  PubMed  Google Scholar 

  61. Henze, K. et al. A nuclear gene of eubacterial origin in Euglena gracilis reflects cryptic endosymbioses during protist evolution. Proc. Natl Acad. Sci. USA 92, 9122–9126 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Stibitz, T. B., Keeling, P. J., & Bhattacharya, D. Symbiotic origin of a novel actin gene in the cryptophyte Pyrenomonas helgolandii. Mol. Biol. Evol. 17, 1731–1738 (2000).

    Article  CAS  PubMed  Google Scholar 

  63. Archibald, J. M., Rogers, M. B., Toop, M., Isheda, K. & Keeling, P. J. Lateral gene transfer and the evolution of plastid-targeted proteins in the secondary plastid-containing alga Bigelowiella natans. Proc. Natl Acad. Sci. USA 100, 7678–7683 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Leister, D. Chloroplast research in the genomics age. Trends Genet. 19, 47–56 (2003).

    Article  CAS  PubMed  Google Scholar 

  65. Gabaldón, T. & Huynen, M. A. Reconstruction of the proto-mitochondrial metabolism. Science 301, 609 (2003).

    Article  PubMed  Google Scholar 

  66. Martin, W. & Schnarrenberger, C. The evolution of the Calvin cycle from prokaryotic to eukaryotic chromosomes: a case study of functional redundancy in ancient pathways through endosymbiosis. Curr. Genet. 32, 1–18 (1997).

    Article  CAS  PubMed  Google Scholar 

  67. Gallois, J. L. et al. The Arabidopsis chloroplast ribosomal protein L21 is encoded by a nuclear gene of mitochondrial origin. Gene 274, 179–185 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Adams, K. L. et al. Genes for two mitochondrial ribosomal proteins in flowering plants are derived from their chloroplast or cytosolic counterparts. Plant Cell 14, 931–943 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Brown, J. R. Ancient horizontal gene transfer. Nature Rev. Genet. 4, 121–132 (2003). An incisive review of gene movement across genomes, including the role of endosymbiotic transfers.

    Article  CAS  PubMed  Google Scholar 

  70. Gil, R. et al. The genome sequence of Blochmannia floridanus: comparative analysis of reduced genomes. Proc. Natl Acad. Sci. USA 100, 9388–9393 (2003). Underscores how reductive evolution in endosymbiotic bacteria leads to massive gene losses through biochemical parasitism of the host.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lister, D. L., Bateman, J. M., Purton, S. & Howe, C. J. DNA transfer from chloroplast to nucleus is much rarer in Chlamydomonas than in tobacco. Gene 316, 33–38 (2003).

    Article  CAS  PubMed  Google Scholar 

  72. Richly, E., Chinnery, P. F. & Leister, D. Evolutionary diversification of mitochondrial proteomes: implications for human disease. Trends Genet. 19, 356–362 (2003).

    Article  CAS  PubMed  Google Scholar 

  73. Richly, E. & Leister, D. An improved prediction of chloroplast proteins reveals diversities and commonalities in the chloroplast proteomes of Arabidopsis and rice. Gene (in the press).

  74. Huh, W. -K. et al. Global analysis of protein localization in budding yeast. Nature 425, 686–691 (2003).

    Article  CAS  PubMed  Google Scholar 

  75. Lange, B. M., Rujan, T., Martin, W. & Croteau, R. Isoprenoid biosynthesis: the evolution of two ancient and distinct pathways across genomes. Proc. Natl Acad. Sci. USA 97, 13172–13177 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Schnarrenberger, C. & Martin, W. Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants: a case study of endosymbiotic gene transfer. Eur. J. Biochem. 269, 868–883 (2002).

    Article  CAS  PubMed  Google Scholar 

  77. Aravind, L., Anantharaman, V. & Iyer, L. M. Evolutionary connections between bacterial and eukaryotic signaling systems: a genomic perspective. Curr. Opin. Microbiol. 6, 490–497 (2003).

    Article  CAS  PubMed  Google Scholar 

  78. Osteryoung, K. W. & Nunnari, J. The division of endosymbiotic organelles. Science 302, 1698–1704 (2003).

    Article  CAS  PubMed  Google Scholar 

  79. McFadden, G. I. & Ralph, S. A. Dynamin: the endosymbiosis ring of power? Proc. Natl Acad. Sci. USA 100, 3557–3559 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Thorsness, P. E. & Fox, T. D. Escape of DNA from the mitochondria to the nucleus in the yeast, Saccharomyces cerevisiae. Nature 346, 376–379 (1990). The initial experimental measurement of the frequency of transfer of DNA between genetic compartments.

    Article  CAS  PubMed  Google Scholar 

  81. Thorsness, P. E. & Fox, T. D. Nuclear mutations in Saccharomyces cerevisiae that affect the escape of DNA from mitochondria to the nucleus. Genetics 134, 21–28 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Shafer, K. S., Hanekamp, T., White, K. H. & Thorsness, P. E. Mechanisms of mitochondrial DNA escape to the nucleus in the yeast Saccharomyces cerevisiae. Curr. Genet. 36, 183–194 (1999).

    Article  CAS  PubMed  Google Scholar 

  83. Huang, C. Y., Ayliffe, M. A. & Timmis, J. N. Direct measurement of the transfer rate of chloroplast DNA into the nucleus. Nature 422, 72–76 (2003). The initial experimental measurement of the frequency of integrative transfer of DNA between chloroplast and nucleus.

    Article  CAS  PubMed  Google Scholar 

  84. Stegemann, S., Hartmann, S., Ruf, S. & Bock, R. High-frequency gene transfer from the chloroplast genome to the nucleus. Proc. Natl Acad. Sci. USA 100, 8828–8833 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Campbell, C. L. & Thorsness, P. E. Escape of mitochondrial DNA to the nucleus in yme1 yeast is mediated by vacuolar-dependent turnover of abnormal mitochondrial compartments. J. Cell Sci. 111, 2455–2464 (1998).

    CAS  PubMed  Google Scholar 

  86. Shay, J. W. & Werbin, H. New evidence for the insertion of mitochondrial DNA into the human genome: significance for cancer and aging. Mutat. Res. 275, 227–235 (1992).

    Article  CAS  PubMed  Google Scholar 

  87. Turner, C. et al. Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer. Hum. Genet. 112, 303–309 (2003).

    PubMed  Google Scholar 

  88. Elo, A. et al. Nuclear genes that encode mitochondrial proteins for DNA and RNA metabolism are clustered in the Arabidopsis genome. Plant Cell 15, 1619–1631 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Richly, E. et al. Covariations in the nuclear chloroplast transcriptome reveal a regulatory master-switch. EMBO Rep. 4, 491–498 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Allen, J. F. The function of genomes in bioenergetic organelles. Phil. Trans. Roy. Soc. B 358, 19–38 (2003). A comprehensive treatment of competing views on the issue of why some genes remain within organelle genomes.

    Article  CAS  Google Scholar 

  91. Pérez-Martínez, X. et al. Subunit II of cytochrome c oxidase in chlamydomonad algae is a heterodimer encoded by two independent nuclear genes. J. Biol. Chem. 276, 11302–11309 (2001)

    Article  PubMed  Google Scholar 

  92. Daley, D. O. et al. Intracellular gene transfer: reduced hydrophobicity facilitates gene transfer for subunit 2 of cytochrome c oxidase. Proc. Natl Acad. Sci. USA 99, 10510–15015 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Pfannschmidt, T., Nilsson, A., & Allen, J. F. Photosynthetic control of chloroplast gene expression. Nature 397, 625–628 (1999).

    Article  CAS  Google Scholar 

  94. Naithani S., Saracco S. A., Butler C. A. & Fox T. D. Interactions among COX1, COX2, and COX3 mRNA-specific translational activator proteins on the inner surface of the mitochondrial inner membrane of Saccharomyces cerevisiae. Mol. Biol. Cell 14, 324–333 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Doolittle, W. F. You are what you eat: a gene transfer ratchet could account for bacterial genes in eukaryotic nuclear genomes. Trends Genet. 14, 307–311 (1998).

    Article  CAS  PubMed  Google Scholar 

  96. Race, H. L., Herrmann, R. G. & Martin, W. Why have organelles retained genomes? Trends Genet. 15, 364–370 (1999).

    Article  CAS  PubMed  Google Scholar 

  97. Devos, K. M., Brown, J. K. M. & Bennetzen J. L. Genome size reduction through illegitimate recombination counteracts genome expansion in Arabidopsis. Genome Res. 12, 1075–1079 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Martin, W. Gene transfers from organelles to the nucleus: frequent and in big chunks. Proc. Natl Acad. Sci. USA 100, 8612–8614 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Maliga, P. Engineering the plastid genome of higher plants. Curr. Opin. Plant Biol. 5, 164–172 (2002).

    Article  CAS  PubMed  Google Scholar 

  100. Daniell, H. & Parkinson, C. L. Jumping genes and containment. Nature Biotechnol. 21, 374–375 (2003). A challenge to the experimental data for gene transfer from chloroplasts by proponents of plastid transgene technology, rebutted head-to-head in reference 101.

    Article  CAS  Google Scholar 

  101. Huang, C. Y., Ayliffe, M. A. & Timmis, J. N. Organelle evolution meets biotechnology. Nature Biotechnol. 21, 489–490 (2003).

    Article  CAS  Google Scholar 

  102. Martin, W. & Russell, M. On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells. Phil. Trans. Roy. Soc. Lond. B 358, 59–85 (2003).

    Article  CAS  Google Scholar 

  103. Doolittle, W. F. et al. How big is the iceberg of which organellar genes in nuclear genomes are but the tip? Philos. Trans. Roy. Soc. Lond. B 358, 39–57 (2003).

    Article  CAS  Google Scholar 

  104. Woese, C., Kandler, O. & Wheelis, M. L. Towards a natural system of organisms: proposal for the domains archaea, bacteria and eucarya. Proc. Natl Acad. Sci. USA 87, 4576–4579 (1990). The current higher-level taxonomic model, with eukaryotes as sisters to archaebacteria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Rivera, M. C., Jain, R., Moore, J. E. & Lake, J. A. Genomic evidence for two functionally distinct gene classes. Proc. Natl Acad. Sci. USA 95, 6239–6244 (1998). A landmark paper that uncovers more eubacterial genes than archaebacterial genes in the yeast genome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Penny, D., Foulds, L. R. & Hendy, M. D. Testing the theory of evolution by comparing phylogenetic trees constructed from five different protein sequences. Nature 297, 197–200 (1982).

    Article  CAS  PubMed  Google Scholar 

  107. Cummings, M. P., Otto, S. P. & Wakeley, J. Sampling properties of DNA-sequence data in phylogenetic analysis. Mol. Biol. Evol. 12, 814–822 (1995).

    CAS  PubMed  Google Scholar 

  108. Embley, T. M. & Hirt, R. P. Early branching eukaryotes? Curr. Opin. Genet. Dev. 8, 655–661 (1998).

    Article  Google Scholar 

  109. Rokas, A., Williams, B. L., King, N. & Carroll, S. B. Genome-scale approaches to resolving incongruence in molecular phylogenies. Nature 425, 798–804 (2003).

    Article  CAS  PubMed  Google Scholar 

  110. Gogarten P. J., Doolittle W. F. & Lawrence J. G. Prokaryotic evolution in light of lateral gene transfer. Mol. Biol. Evol. 19, 2226–2238 (2002).

    Article  CAS  PubMed  Google Scholar 

  111. Hedges, S. B. et al. A genomic timescale for the origin of eukaryotes. BMC Evol. Biol. 1, 4 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hartman, H. & Fedorov, A. The origin of the eukaryotic cell: a genomic investigation. Proc. Natl Acad. Sci. USA 99, 1420–1425 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Stechmann, A. & Cavalier-Smith, T. Rooting the eukaryote tree by using a derived gene fusion. Science 297, 89–91 (2002). A milestone relating to the issue of which eukaryotes might be the most ancient.

    Article  CAS  PubMed  Google Scholar 

  114. Kondo, N., Nikoh, N., Ijichi, N., Shimada, M. & Fukatsu, T. Genome fragment of Wolbachia endosymbiont transferred to X chromosome of host insect. Proc. Natl Acad. Sci. USA 99, 14280–14285 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Neupert, W. Protein import into mitochondria. Ann. Rev. Biochem. 66, 683–717 (1997).

    Article  Google Scholar 

  116. Martin, W. & Müller, M. The hydrogen hypothesis for the first eukaryote. Nature 392, 37–41 (1998).

    Article  CAS  PubMed  Google Scholar 

  117. Soll, J. Protein import into chloroplasts. Curr. Opin. Plant. Biol. 5, 529–535 (2002).

    Article  CAS  PubMed  Google Scholar 

  118. Bendich, A. J. & Drlica, K. Prokaryotic and eukaryotic chromosomes: what's the difference? BioEssays 22, 481–486 (2000). An enlightening survey of chromosome attributes in prokaryotes and eukaryotes.

    Article  CAS  PubMed  Google Scholar 

  119. Birky, C. W. The inheritance of genes in mitochondria and chloroplasts: laws, mechanisms and models. Annu. Rev. Genet. 35, 125–148 (2001).

    Article  CAS  PubMed  Google Scholar 

  120. Martin, W., Hoffmeister, M., Rotte, C. & Henze, K. An overview of endosymbiotic models for the origins of eukaryotes, their ATP-producing organelles (mitochondria and hydrogenosomes), and their heterotrophic lifestyle. Biol. Chem. 382, 1521–1539 (2001).

    Article  CAS  PubMed  Google Scholar 

  121. Butterfield, N. J. Bangiomorpha pubescens n. gen., n. sp.: implications for the evolution of sex, multicellularity, and the Mesoproterozoic/ Neoproterozoic radiation of eukaryotes. Paleobiology 26, 386–404 (2000). A fossil red algae of 1. 2 billion years of age anchors plant evolution in the Precambrian age.

    Article  Google Scholar 

Download references

Acknowledgements

We thank M. Limpert for help in preparing the manuscript, the Australian Research Council, the Australian–German Joint Research Cooperation Scheme and the Deutsche Forschungsgemeinschaft for financial support, and D. Leister for valuable discussions and permission to modify published figures. Countless individual report on numts, nupts and eukaryotic genes that were acquired from organelles are available; we apologize to all for having to focus on selected and more recent work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jeremy N. Timmis.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

TAIR

rps10

FURTHER INFORMATION

CyanoBase

DOE Joint Genome Institute

The Institute for Genomic Research

The Organelle Genome Megasequencing Program

Glossary

CYANOBACTERIA

The group of pigmented, photosynthetic bacteria that contains the endosymbiont ancestors of chloroplasts.

α-PROTEOBACTERIA

A subgroup of gram-negative bacteria, often called the purple bacteria, that are thought to be the endosymbiont ancestors of mitochondria.

DISOMIC

The condition in which there are two sets of similar (homologous) chromosomes, such that there are two alleles for each gene locus. These homologous chromosomes pair at meiosis and their segregation and transmission results in Mendelian inheritance.

HAPLOID

The condition in which there is only a single chromosome, or set of chromosomes, such that all loci are represented by only a single allele.

CYTOPLASMIC ORGANELLES

Here, confined to mean mitochondria and plastids.

PROMISCUOUS DNA

DNA that is present in more than one genetic compartment of the eukaryotic cell.

ARCHAEBACTERIA

An ancient group of organisms that have ribosomes and cell membranes that distinguish them from eubacteria. They sometimes show environmentally extreme ecology.

NUMT

An acronym to describe nuclear integrants of mitochondrial DNA.

INTEGRANT

Here, used to describe nuclear tracts of DNA that resemble plastid DNA or mitochondrial DNA.

NUPT

An acronym to describe nuclear integrants of plastid DNA.

TRANSIT PEPTIDE

A peptide sequence, often at the N-terminus of a precursor protein, that directs a gene product to its specific cellular destination.

MUTATIONAL DECAY

The process that describes the random changes that might occur in a DNA sequence in the absence of selection pressure.

PROTIST

A single-celled eukaryote.

PHYLOGENETICS

Reconstruction of the evolutionary relationships between sequences using any of a variety of inference methods.

PRODUCT SPECIFICITY COROLLARY

The situation in which the product of a gene that is donated by a cytoplasmic organelle to the nucleus is expected to be returned to that organelle.

EPISOME

A unit of genetic material that is composed of a series of genes that sometimes has an independent existence in a host cell and at other times is integrated into a chromosome of the cell, replicating itself along with the chromosome.

BIOLISTIC TRANSFORMATION

A commonly used transformation method in which metal beads are coated with gene contructs and shot into cells.

LEAF EXPLANTS

Small sterile sections of leaf or other plant tissue from which whole plants might sometimes be regenerated.

UNIPARENTAL INHERITANCE

The mode of inheritance that generally characterizes the genes of cytoplasmic organelles in which only one of the two sexual partners contributes to the offspring.

TRANSPLASTOME

The condition of a plastid genome after the insertion of non-native genes.

MT STRAIN

One of the two mating types (the other is mt+) of Chlamydomonas reinhardtii; one of each is required to form a zygote.

RNA EDITING

Changes in the RNA sequence after transcription is completed. Examples include modification of C to U or of A to I by deamination, or insertion and/or deletion of particular bases.

PROMOTER TRAP

A genetic engineering technique that involves randomly inserting into the genome constructs that encode an easily detectable marker, such as GFP, but contain no promoter sequences. Marker expression is only detected when the construct lands near an endogenous genomic promoter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Timmis, J., Ayliffe, M., Huang, C. et al. Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat Rev Genet 5, 123–135 (2004). https://doi.org/10.1038/nrg1271

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg1271

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing