Cytonuclear integration and co-evolution


The partitioning of genetic material between the nucleus and cytoplasmic (mitochondrial and plastid) genomes within eukaryotic cells necessitates coordinated integration between these genomic compartments, with important evolutionary and biomedical implications. Classic questions persist about the pervasive reduction of cytoplasmic genomes via a combination of gene loss, transfer and functional replacement — and yet why they are almost always retained in some minimal form. One striking consequence of cytonuclear integration is the existence of ‘chimeric’ enzyme complexes composed of subunits encoded in two different genomes. Advances in structural biology and comparative genomics are yielding important insights into the evolution of such complexes, including correlated sequence changes and recruitment of novel subunits. Thus, chimeric cytonuclear complexes provide a powerful window into the mechanisms of molecular co-evolution.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Variation in mitochondrial gene content across eukaryotic lineages.
Fig. 2: Opposite trends in the cytonuclear movement of genes versus gene products.
Fig. 3: Acquisition of supernumerary subunits in chimeric cytonuclear enzyme complexes.


  1. 1.

    Gray, M. W. & Archibald, J. M. in Genomics of Chloroplasts and Mitochondria, Advances in Photosynthesis and Respiration (eds Bock, R. & Knoop, V.) 1–30 (Springer, 2012).

  2. 2.

    Burton, R. S. & Barreto, F. S. A disproportionate role for mtDNA in Dobzhansky-Muller incompatibilities? Mol. Ecol. 21, 4942–4957 (2012). This review argues for a special role of cytonuclear interactions in the process of speciation and summarizes extensive work in Tigriopus copepods, a classic system for mitonuclear biology.

    CAS  PubMed  Google Scholar 

  3. 3.

    Eyre-Walker, A. Mitochondrial replacement therapy: are mito-nuclear interactions likely to be a problem? Genetics 205, 1365–1372 (2017). The author of this paper argues on both theoretical and empirical grounds that the effects of mitonuclear incompatibilities on reproductive isolation and the risks associated with mitochondrial replacement therapy have been exaggerated.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Hill, G. E. The mitonuclear compatibility species concept. Auk 134, 393–409 (2017).

    Google Scholar 

  5. 5.

    Sloan, D. B., Havird, J. C. & Sharbrough, J. The on-again, off-again relationship between mitochondrial genomes and species boundaries. Mol. Ecol. 26, 2212–2236 (2017).

    PubMed  Google Scholar 

  6. 6.

    Dowling, D. K. Evolutionary perspectives on the links between mitochondrial genotype and disease phenotype. Biochim. Biophys. Acta 1840, 1393–1403 (2014).

    CAS  PubMed  Google Scholar 

  7. 7.

    Reinhardt, K., Dowling, D. K. & Morrow, E. H. Mitochondrial replacement, evolution, and the clinic. Science 341, 1345–1346 (2013).

    PubMed  Google Scholar 

  8. 8.

    Chinnery, P. F. et al. The challenges of mitochondrial replacement. PLOS Genet. 10, e1004315 (2014).

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Dobler, R., Dowling, D. K., Morrow, E. H. & Reinhardt, K. A systematic review and meta-analysis reveals pervasive effects of germline mitochondrial replacement on components of health. Hum. Reprod. Update (2018). This meta-analysis reports evidence that mitonuclear mismatches can have detrimental consequences, and the authors contend that this is an important consideration for applications of mitochondrial replacement therapy in humans.

    Article  PubMed  Google Scholar 

  10. 10.

    Rand, D. M., Haney, R. A. & Fry, A. J. Cytonuclear coevolution: the genomics of cooperation. Trends Ecol. Evol. 19, 645–653 (2004).

    PubMed  Google Scholar 

  11. 11.

    Paila, Y. D., Richardson, L. G. L. & Schnell, D. J. New insights into the mechanism of chloroplast protein import and its integration with protein quality control, organelle biogenesis and development. J. Mol. Biol. 427, 1038–1060 (2015).

    CAS  PubMed  Google Scholar 

  12. 12.

    Chan, K. X., Phua, S. Y., Crisp, P., McQuinn, R. & Pogson, B. J. Learning the languages of the chloroplast: retrograde signaling and beyond. Annu. Rev. Plant Biol. 67, 25–53 (2016).

    CAS  PubMed  Google Scholar 

  13. 13.

    Quirós, P. M., Mottis, A. & Auwerx, J. Mitonuclear communication in homeostasis and stress. Nat. Rev. Mol. Cell Biol. 17, 213–226 (2016).

    PubMed  Google Scholar 

  14. 14.

    Wiedemann, N. & Pfanner, N. Mitochondrial machineries for protein import and assembly. Annu. Rev. Biochem. 86, 685–714 (2017).

    CAS  Google Scholar 

  15. 15.

    Curtis, B. A. et al. Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs. Nature 492, 59–65 (2012).

    CAS  PubMed  Google Scholar 

  16. 16.

    Nowack, E. C. & Melkonian, M. Endosymbiotic associations within protists. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 699–712 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    McCutcheon, J. P. & Moran, N. A. Extreme genome reduction in symbiotic bacteria. Nat. Rev. Microbiol. 10, 13–26 (2012).

    CAS  Google Scholar 

  18. 18.

    Adams, K. L. & Palmer, J. D. Evolution of mitochondrial gene content: gene loss and transfer to the nucleus. Mol. Phylogenet. Evol. 29, 380–395 (2003).

    CAS  Google Scholar 

  19. 19.

    Timmis, J. N., Ayliffe, M. A., Huang, C. Y. & Martin, W. Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat. Rev. Genet. 5, 123–135 (2004).

    CAS  Google Scholar 

  20. 20.

    Gray, M. W. Mitochondrial evolution. Cold Spring Harb. Perspect. Biol. 4, a011403 (2012).

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Huynen, M. A., Duarte, I. & Szklarczyk, R. Loss, replacement and gain of proteins at the origin of the mitochondria. Biochim. Biophys. Acta. 1827, 224–231 (2013).

    CAS  PubMed  Google Scholar 

  22. 22.

    Johnston, I. G. & Williams, B. P. Evolutionary inference across eukaryotes identifies specific pressures favoring mitochondrial gene retention. Cell Systems 2, 101–111 (2016). This analysis infers the relative timing of gene losses from mitogenomes in different eukaryotic lineages and identifies the features that favour retention of specific genes in the mitogenome.

    CAS  PubMed  Google Scholar 

  23. 23.

    Kannan, S., Rogozin, I. B. & Koonin, E. V. MitoCOGs: clusters of orthologous genes from mitochondria and implications for the evolution of eukaryotes. BMC Evol. Biol. 14, 237 (2014).

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Janouškovec, J. et al. A new lineage of eukaryotes illuminates early mitochondrial genome reduction. Curr. Biol. 27, 3717–3724 (2017). This study includes a reannotation of mitochondrial gene content across diverse eukaryotic lineages, allowing for the reconstruction of heterogeneous rates of gene loss through time and across lineages.

    PubMed  Google Scholar 

  25. 25.

    Wang, Z. & Wu, M. Phylogenomic reconstruction indicates mitochondrial ancestor was an energy parasite. PLOS One 9, e110685 (2014).

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Petersen, J. et al. Chromera velia, endosymbioses and the rhodoplex hypothesis — plastid evolution in cryptophytes, alveolates, stramenopiles, and haptophytes (CASH lineages). Genome Biol. Evol. 6, 666–684 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Flegontov, P. et al. Divergent mitochondrial respiratory chains in phototrophic relatives of apicomplexan parasites. Mol. Biol. Evol. 32, 1115–1131 (2015).

    CAS  PubMed  Google Scholar 

  28. 28.

    Burger, G., Gray, M. W., Forget, L. & Lang, B. F. Strikingly bacteria-like and gene-rich mitochondrial genomes throughout jakobid protists. Genome Biol. Evol. 5, 418–438 (2013).

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Pett, W. & Lavrov, D. V. Cytonuclear interactions in the evolution of animal mitochondrial tRNA metabolism. Genome Biol. Evol. 7, 2089–2101 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Salinas-Giegé, T., Giegé, R. & Giegé, P. tRNA biology in mitochondria. Int. J. Mol. Sci. 16, 4518–4559 (2015).

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    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). This classic study provides extensive documentation of the variation in mitochondrial gene content across angiosperms, revealing a rapid and ongoing process of EGT.

    CAS  PubMed  Google Scholar 

  32. 32.

    Barbrook, A. C., Voolstra, C. R. & Howe, C. J. The chloroplast genome of a Symbiodinium sp. clade C3 isolate. Protist 165, 1–13 (2014).

    CAS  PubMed  Google Scholar 

  33. 33.

    Del Cortona, A. et al. The plastid genome in Cladophorales green algae is encoded by hairpin chromosomes. Curr. Biol. 27, 3771–3782 (2017).

    PubMed  Google Scholar 

  34. 34.

    Maier, U.-G. et al. Massively convergent evolution for ribosomal protein gene content in plastid and mitochondrial genomes. Genome Biol. Evol. 5, 2318–2329 (2013).

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Pont-Kingdon, G. et al. Mitochondrial DNA of the coral Sarcophyton glaucum contains a gene for a homologue of bacterial MutS: a possible case of gene transfer from the nucleus to the mitochondrion. J. Mol. Evol. 46, 419–431 (1998).

    CAS  PubMed  Google Scholar 

  36. 36.

    Knie, N., Polsakiewicz, M. & Knoop, V. Horizontal gene transfer of chlamydial-like tRNA genes into early vascular plant mitochondria. Mol. Biol. Evol. 32, 629–634 (2014).

    PubMed  Google Scholar 

  37. 37.

    Milani, L., Ghiselli, F., Maurizii, M. G., Nuzhdin, S. V. & Passamonti, M. Paternally transmitted mitochondria express a new gene of potential viral origin. Genome Biol. Evol. 6, 391–405 (2014).

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Qiu, Y., Filipenko, S. J., Darracq, A. & Adams, K. L. Expression of a transferred nuclear gene in a mitochondrial genome. Curr. Plant Biol. 1, 68–72 (2014).

    Google Scholar 

  39. 39.

    Korovesi, A. G., Ntertilis, M. & Kouvelis, V. N. Mt-rps3 is an ancient gene which provides insight into the evolution of fungal mitochondrial genomes. Mol. Phylogenet. Evol. 127, 74–86 (2018).

    CAS  PubMed  Google Scholar 

  40. 40.

    Ruck, E. C., Nakov, T., Jansen, R. K., Theriot, E. C. & Alverson, A. J. Serial gene losses and foreign DNA underlie size and sequence variation in the plastid genomes of diatoms. Genome Biol. Evol. 6, 644–654 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Yurchenko, T., Ševčíková, T., Strnad, H., Butenko, A. & Eliáš, M. The plastid genome of some eustigmatophyte algae harbours a bacteria-derived six-gene cluster for biosynthesis of a novel secondary metabolite. Open Biol. 6, 160249 (2016).

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Amikura, R., Kashikawa, M., Nakamura, A. & Kobayashi, S. Presence of mitochondria-type ribosomes outside mitochondria in germ plasm of Drosophila embryos. Proc. Natl Acad. Sci. USA 98, 9133–9138 (2001).

    CAS  PubMed  Google Scholar 

  43. 43.

    Villegas, J., Araya, P., Bustos-Obregon, E. & Burzio, L. O. Localization of the 16S mitochondrial rRNA in the nucleus of mammalian spermatogenic cells. Mol. Hum. Reprod. 8, 977–983 (2002).

    CAS  PubMed  Google Scholar 

  44. 44.

    Zheng, Z., Li, H., Zhang, Q., Yang, L. & Qi, H. Unequal distribution of 16S mtrRNA at the 2-cell stage regulates cell lineage allocations in mouse embryos. Reproduction 151, 351–367 (2016).

    CAS  PubMed  Google Scholar 

  45. 45.

    Maniataki, E. & Mourelatos, Z. Human mitochondrial tRNAMet is exported to the cytoplasm and associates with the Argonaute 2 protein. RNA 11, 849–852 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Cognat, V. et al. The nuclear and organellar tRNA-derived RNA fragment population in Arabidopsis thaliana is highly dynamic. Nucleic Acids Res. 45, 3460–3472 (2017).

    CAS  PubMed  Google Scholar 

  47. 47.

    Landerer, E. et al. Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells. Cell. Oncol. 34, 297–305 (2011).

    CAS  Google Scholar 

  48. 48.

    Dietrich, A., Wallet, C., Iqbal, R. K., Gualberto, J. M. & Lotfi, F. Organellar non-coding RNAs: emerging regulation mechanisms. Biochimie 117, 48–62 (2015).

    CAS  PubMed  Google Scholar 

  49. 49.

    Pozzi, A., Plazzi, F., Milani, L., Ghiselli, F. & Passamonti, M. SmithRNAs: could mitochondria “bend” nuclear regulation? Mol. Biol. Evol. 34, 1960–1973 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Lee, C., Yen, K. & Cohen, P. Humanin: a harbinger of mitochondrial-derived peptides? Trends Endocrinol. Metabolism 24, 222–228 (2013).

    CAS  Google Scholar 

  51. 51.

    Lee, C. et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell. Metabolism 21, 443–454 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Gray, M. W. Mosaic nature of the mitochondrial proteome: Implications for the origin and evolution of mitochondria. Proc. Natl Acad. Sci. USA 112, 10133–10138 (2015). This paper provides a broad review of mitochondrial evolution, arguing for diverse phylogenetic sources contributing to the origins of the mitochondrial proteome in eukaryotes.

    CAS  PubMed  Google Scholar 

  53. 53.

    Karlberg, O., Canback, B., Kurland, C. G. & Andersson, S. G. The dual origin of the yeast mitochondrial proteome. Yeast 17, 170–187 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Gabaldón, T. & Huynen, M. A. From endosymbiont to host-controlled organelle: the hijacking of mitochondrial protein synthesis and metabolism. PLOS Computat. Biol. 3, e219 (2007).

    Google Scholar 

  55. 55.

    Szklarczyk, R. & Huynen, M. A. Mosaic origin of the mitochondrial proteome. Proteomics 10, 4012–4024 (2010).

    CAS  PubMed  Google Scholar 

  56. 56.

    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). This paper lays out the hypothesis for a non-adaptive gene transfer ratchet as an explanation for the frequent replacement of pre-existing host functions by endosymbiotic genes.

    CAS  PubMed  Google Scholar 

  57. 57.

    Thorsness, P. E. & Fox, T. D. Escape of DNA from mitochondria to the nucleus in Saccharomyces cerevisiae. Nature 346, 376–379 (1990).

    CAS  PubMed  Google Scholar 

  58. 58.

    Hazkani-Covo, E., Zeller, R. M. & Martin, W. Molecular poltergeists: mitochondrial DNA copies (numts) in sequenced nuclear genomes. PLOS Genet. 6, e1000834 (2010).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Dolezal, P., Likic, V., Tachezy, J. & Lithgow, T. Evolution of the molecular machines for protein import into mitochondria. Science 313, 314–318 (2006).

    CAS  PubMed  Google Scholar 

  60. 60.

    Shi, L.-X. & Theg, S. M. The chloroplast protein import system: from algae to trees. Biochim. Biophys. Acta-Mol. Cell Res. 1833, 314–331 (2013).

    CAS  Google Scholar 

  61. 61.

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

    CAS  PubMed  Google Scholar 

  62. 62.

    Timmis, J. N. & Scott, N. S. Sequence homology between spinach nuclear and chloroplast genomes. Nature 305, 65–67 (1983).

    CAS  Google Scholar 

  63. 63.

    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 

  64. 64.

    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).

    CAS  PubMed  Google Scholar 

  65. 65.

    Huang, C. Y., Ayliffe, M. A. & Timmis, J. N. Simple and complex nuclear loci created by newly transferred chloroplast DNA in tobacco. Proc. Natl Acad. Sci. USA 101, 9710–9715 (2004).

    CAS  PubMed  Google Scholar 

  66. 66.

    Fuentes, I., Karcher, D. & Bock, R. Experimental reconstruction of the functional transfer of intron-containing plastid genes to the nucleus. Curr. Biol. 22, 763–771 (2012).

    CAS  PubMed  Google Scholar 

  67. 67.

    Hazkani-Covo, E. & Martin, W. F. Quantifying the number of independent organelle DNA insertions in genome evolution and human health. Genome Biol. Evol. 9, 1190–1203 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    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).

    CAS  PubMed  Google Scholar 

  69. 69.

    Ricchetti, M., Fairhead, C. & Dujon, B. Mitochondrial DNA repairs double-strand breaks in yeast chromosomes. Nature 402, 96–100 (1999).

    CAS  PubMed  Google Scholar 

  70. 70.

    Richly, E. & Leister, D. NUPTs in sequenced eukaryotes and their genomic organization in relation to NUMTs. Mol. Biol. Evol. 21, 1972–1980 (2004).

    CAS  PubMed  Google Scholar 

  71. 71.

    Smith, D. R., Crosby, K. & Lee, R. W. Correlation between nuclear plastid DNA abundance and plastid number supports the limited transfer window hypothesis. Genome Biol. Evol. 3, 365–371 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Barbrook, A. C., Howe, C. J. & Purton, S. Why are plastid genomes retained in non-photosynthetic organisms? Trends Plant Sci. 11, 101–108 (2006).

    CAS  PubMed  Google Scholar 

  73. 73.

    Wu, Z. et al. Mitochondrial retroprocessing promoted functional transfers of rpl5 to the nucleus in grasses. Mol. Biol. Evol. 34, 2340–2354 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Adams, K. L. et al. Intracellular gene transfer in action: dual transcription and multiple silencings of nuclear and mitochondrial cox2 genes in legumes. Proc. Natl Acad. Sci. USA 96, 13863–13868 (1999).

    CAS  PubMed  Google Scholar 

  75. 75.

    Liu, S. L., Zhuang, Y., Zhang, P. & Adams, K. L. Comparative analysis of structural diversity and sequence evolution in plant mitochondrial genes transferred to the nucleus. Mol. Biol. Evol. 26, 875–891 (2009).

    PubMed  Google Scholar 

  76. 76.

    Bonen, L. & Calixte, S. Comparative analysis of bacterial-origin genes for plant mitochondrial ribosomal proteins. Mol. Biol. Evol. 23, 701–712 (2006).

    CAS  PubMed  Google Scholar 

  77. 77.

    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).

    CAS  PubMed  Google Scholar 

  78. 78.

    Smith, D. R. & Keeling, P. J. Mitochondrial and plastid genome architecture: Reoccurring themes, but significant differences at the extremes. Proc. Natl Acad. Sci. USA 112, 10177–10184 (2015).

    CAS  PubMed  Google Scholar 

  79. 79.

    Timmis, J. N. Endosymbiotic evolution: RNA intermediates in endosymbiotic gene transfer. Curr. Biol. 22, R296–R298 (2012).

    CAS  PubMed  Google Scholar 

  80. 80.

    Sheppard, A. E. et al. Introducing an RNA editing requirement into a plastid-localised transgene reduces but does not eliminate functional gene transfer to the nucleus. Plant Mol. Biol. 76, 299–309 (2011).

    CAS  PubMed  Google Scholar 

  81. 81.

    Henze, K. & Martin, W. How do mitochondrial genes get into the nucleus? Trends Genet. 17, 383–387 (2001).

    CAS  PubMed  Google Scholar 

  82. 82.

    Grewe, F., Zhu, A. & Mower, J. P. Loss of a trans-splicing nad1 intron from Geraniaceae and transfer of the maturase gene matR to the nucleus in Pelargonium. Genome Biol. Evol. 8, 3193–3201 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Allen, J. F. & Raven, J. A. Free-radical-induced mutation versus redox regulation: costs and benefits of genes in organelles. J. Mol. Evol. 42, 482–492 (1996).

    CAS  PubMed  Google Scholar 

  84. 84.

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

    CAS  PubMed  Google Scholar 

  85. 85.

    Brandvain, Y. & Wade, M. J. The functional transfer of genes from the mitochondria to the nucleus: the effects of selection, mutation, population size and rate of self-fertilization. Genetics 182, 1129–1139 (2009).

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Cooper, B. S., Burrus, C. R., Ji, C., Hahn, M. W. & Montooth, K. L. Similar efficacies of selection shape mitochondrial and nuclear genes in both Drosophila melanogaster and Homo sapiens. G3 5, 2165–2176 (2015).

    CAS  PubMed  Google Scholar 

  87. 87.

    Christie, J. R. & Beekman, M. Uniparental inheritance promotes adaptive evolution in cytoplasmic genomes. Mol. Biol. Evol. 34, 677–691 (2016).

    PubMed Central  Google Scholar 

  88. 88.

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

    CAS  PubMed  Google Scholar 

  89. 89.

    Adams, K. L., Daley, D. O., Whelan, J. & Palmer, J. D. Genes for two mitochondrial ribosomal proteins in flowering plants are derived from their chloroplast or cytosolic counterparts. Plant Cell 14, 931–943 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Duchêne, A.-M., Pujol, C. & Maréchal-Drouard, L. Import of tRNAs and aminoacyl-tRNA synthetases into mitochondria. Curr. Genet. 55, 1–18 (2009).

    PubMed  Google Scholar 

  91. 91.

    Carrie, C. & Small, I. A reevaluation of dual-targeting of proteins to mitochondria and chloroplasts. Biochim. Biophys. Acta. 1833, 253–259 (2013).

    CAS  PubMed  Google Scholar 

  92. 92.

    Woese, C. R., Olsen, G. J., Ibba, M. & Söll, D. Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process. Microbiol. Mol. Biol. Rev. 64, 202–236 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Meiklejohn, C. D. et al. An Incompatibility between a mitochondrial tRNA and its nuclear-encoded tRNA synthetase compromises development and fitness in Drosophila. PLOS Genet. 9, e1003238 (2013). This study provides a detailed characterization of the incompatibilities arising from individual substitutions in a nuclear-encoded aaRS and a mitochondrial-encoded tRNA.

    CAS  PubMed  Google Scholar 

  94. 94.

    Harrison, J. S. & Burton, R. S. Tracing hybrid incompatibilities to single amino acid substitutions. Mol. Biol. Evol. 23, 559–564 (2006).

    CAS  PubMed  Google Scholar 

  95. 95.

    Osada, N. & Akashi, H. Mitochondrial-nuclear interactions and accelerated compensatory evolution: evidence from the primate cytochrome C oxidase complex. Mol. Biol. Evol. 29, 337 (2012). This study analyses both the structural positions and relative timing of amino acid substitutions in a mitonuclear enzyme complex to infer the co-evolutionary effects of mutation pressure in the mitochondrial genome.

    CAS  PubMed  Google Scholar 

  96. 96.

    van der Sluis, E. O. et al. Parallel structural evolution of mitochondrial ribosomes and OXPHOS complexes. Genome Biol. Evol. 7, 1235–1251 (2015). This study models structural interactions involving supernumerary subunits in mitonuclear enzyme complexes and advances the hypothesis that these subunits were recruited to compensate for destabilizing changes in mitochondrial-encoded subunits.

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Barreto, F. S. & Burton, R. S. Evidence for compensatory evolution of ribosomal proteins in response to rapid divergence of mitochondrial rRNA. Mol. Biol. Evol. 30, 310–314 (2013).

    CAS  PubMed  Google Scholar 

  98. 98.

    Willett, C. S. & Burton, R. S. Evolution of interacting proteins in the mitochondrial electron transport system in a marine copepod. Mol. Biol. Evol. 21, 443–453 (2004).

    CAS  PubMed  Google Scholar 

  99. 99.

    Grossman, L. I., Wildman, D. E., Schmidt, T. R. & Goodman, M. Accelerated evolution of the electron transport chain in anthropoid primates. Trends Genet. 20, 578–585 (2004).

    CAS  PubMed  Google Scholar 

  100. 100.

    Zhang, F. & Broughton, R. E. Mitochondrial-nuclear interactions: compensatory evolution or variable functional constraint among vertebrate oxidative phosphorylation genes? Genome Biol. Evol. 5, 1781–1791 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Sloan, D. B., Triant, D. A., Wu, M. & Taylor, D. R. Cytonuclear interactions and relaxed selection accelerate sequence evolution in organelle ribosomes. Mol. Biol. Evol. 31, 673–682 (2014). This paper is one of many recent studies to compare closely related species with dramatically different rates of cytoplasmic genome evolution in order to infer co-evolutionary consequences in the nucleus.

    CAS  PubMed  Google Scholar 

  102. 102.

    Adrion, J. R., White, P. S. & Montooth, K. L. The roles of compensatory evolution and constraint in aminoacyl tRNA synthetase evolution. Mol. Biol. Evol. 33, 152 (2016).

    CAS  PubMed  Google Scholar 

  103. 103.

    Rockenbach, K. D. et al. Positive selection in rapidly evolving plastid-nuclear enzyme complexes. Genetics 204, 1507–1522 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Havird, J. C., Whitehill, N. S., Snow, C. D. & Sloan, D. B. Conservative and compensatory evolution in oxidative phosphorylation complexes of angiosperms with highly divergent rates of mitochondrial genome evolution. Evolution 69, 3069–3081 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Weng, M. L., Ruhlman, T. A. & Jansen, R. K. Plastid-nuclear interaction and accelerated coevolution in plastid ribosomal genes in Geraniaceae. Genome Biol. Evol. 8, 1824–1838 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Zhang, J., Ruhlman, T. A., Sabir, J., Blazier, J. C. & Jansen, R. K. Coordinated rates of evolution between interacting plastid and nuclear genes in Geraniaceae. Plant Cell 27, 563–573 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Li, Y. et al. The molecular evolutionary dynamics of oxidative phosphorylation (OXPHOS) genes in Hymenoptera. BMC Evol. Biol. 17, 269 (2017).

    PubMed  PubMed Central  Google Scholar 

  108. 108.

    Havird, J. C., Trapp, P., Miller, C., Bazos, I. & Sloan, D. B. Causes and consequences of rapidly evolving mtDNA in a plant lineage. Genome Biol. Evol. 9, 323–336 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Yan, Z., Ye, G.-y & Werren, J. Evolutionary rate coevolution between mitochondria and mitochondria-associated nuclear-encoded proteins in insects. Preprint at bioRxiv (2018).

    Article  Google Scholar 

  110. 110.

    Ellison, C. K. & Burton, R. S. Disruption of mitochondrial function in interpopulation hybrids of Tigriopus californicus. Evolution 60, 1382–1391 (2006).

    CAS  PubMed  Google Scholar 

  111. 111.

    Ehrlich, P. R. & Raven, P. H. Butterflies and plants: a study in coevolution. Evolution 18, 586–608 (1964).

    Google Scholar 

  112. 112.

    Janzen, D. H. When is it coevolution? Evolution 34, 611–612 (1980).

    PubMed  Google Scholar 

  113. 113.

    Desmond, E., Brochier-Armanet, C., Forterre, P. & Gribaldo, S. On the last common ancestor and early evolution of eukaryotes: reconstructing the history of mitochondrial ribosomes. Res. Microbiol. 162, 53–70 (2011).

    CAS  PubMed  Google Scholar 

  114. 114.

    Smits, P., Smeitink, J. A., van den Heuvel, L. P., Huynen, M. A. & Ettema, T. J. Reconstructing the evolution of the mitochondrial ribosomal proteome. Nucleic Acids Res. 35, 4686–4703 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Berry, S. Endosymbiosis and the design of eukaryotic electron transport. Biochim. Biophys. Acta. 1606, 57–72 (2003).

    CAS  PubMed  Google Scholar 

  116. 116.

    Sharma, M. R. et al. Cryo-EM study of the spinach chloroplast ribosome reveals the structural and functional roles of plastid-specific ribosomal proteins. Proc. Natl Acad. Sci. USA 104, 19315–19320 (2007).

    CAS  PubMed  Google Scholar 

  117. 117.

    Senkler, J., Senkler, M. & Braun, H. P. Structure and function of complex I in animals and plants–a comparative view. Physiol. Plantarum 161, 6–15 (2017).

    CAS  Google Scholar 

  118. 118.

    Elurbe, D. M. & Huynen, M. A. The origin of the supernumerary subunits and assembly factors of complex I: a treasure trove of pathway evolution. Biochim. Biophys. Acta. 1857, 971–979 (2016). This review provides a detailed documentation of the history of supernumerary subunit acquisition in mitochondrial OXPHOS complex I.

    CAS  PubMed  Google Scholar 

  119. 119.

    O’Brien, T. W. Evolution of a protein-rich mitochondrial ribosome: implications for human genetic disease. Gene 286, 73–79 (2002).

    PubMed  Google Scholar 

  120. 120.

    Sharma, M. R. et al. Structure of the mammalian mitochondrial ribosome reveals an expanded functional role for its component proteins. Cell 115, 97–108 (2003).

    CAS  PubMed  Google Scholar 

  121. 121.

    Stroud, D. A. et al. Accessory subunits are integral for assembly and function of human mitochondrial complex I. Nature 538, 123 (2016). This study includes a systematic analysis of the effects of knocking out individual supernumerary subunits in mitochondrial complex I, revealing common roles in complex assembly and stability.

    CAS  PubMed  Google Scholar 

  122. 122.

    Fiedorczuk, K. et al. Atomic structure of the entire mammalian mitochondrial complex I. Nature 538, 406–410 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123.

    Zhu, J., Vinothkumar, K. R. & Hirst, J. Structure of mammalian respiratory complex I. Nature 536, 354 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Wu, M., Gu, J., Guo, R., Huang, Y. & Yang, M. Structure of mammalian respiratory supercomplex I1III2IV1. Cell 167, 1598–1609 (2016).

    CAS  PubMed  Google Scholar 

  125. 125.

    Guo, R., Zong, S., Wu, M., Gu, J. & Yang, M. Architecture of human mitochondrial respiratory megacomplex I2III2IV2. Cell 170, 1247–1257 (2017).

    CAS  Google Scholar 

  126. 126.

    Gu, J. et al. The architecture of the mammalian respirasome. Nature 537, 639 (2016).

    CAS  Google Scholar 

  127. 127.

    Davies, K. M., Blum, T. B. & Kühlbrandt, W. Conserved in situ arrangement of complex I and III2 in mitochondrial respiratory chain supercomplexes of mammals, yeast, and plants. Proc. Natl Acad. Sci. USA 115, 3024–3029 (2018). This structural study compares mitochondrial OXPHOS supercomplex assemblies across diverse eukaryotes, revealing widely conserved features of these higher-order structures.

    CAS  PubMed  Google Scholar 

  128. 128.

    Genova, M. L. & Lenaz, G. Functional role of mitochondrial respiratory supercomplexes. Biochim. Biophys. Acta. 1837, 427–443 (2014).

    CAS  PubMed  Google Scholar 

  129. 129.

    Angerer, H. et al. A scaffold of accessory subunits links the peripheral arm and the distal proton-pumping module of mitochondrial complex I. Biochem. J. 437, 279–288 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. 130.

    Hirst, J. Why does mitochondrial complex I have so many subunits? Biochem. J. 437, e1–e3 (2011).

    CAS  PubMed  Google Scholar 

  131. 131.

    Melber, A. & Winge, D. R. Inner secrets of the respirasome. Cell 167, 1450–1452 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. 132.

    Cogliati, S. et al. Mechanism of super-assembly of respiratory complexes III and IV. Nature 539, 579–582 (2016).

    CAS  PubMed  Google Scholar 

  133. 133.

    Hayashi, T. et al. Higd1a is a positive regulator of cytochrome c oxidase. Proc. Natl Acad. Sci. USA 112, 1553–1558 (2015).

    CAS  PubMed  Google Scholar 

  134. 134.

    Chaban, Y., Boekema, E. J. & Dudkina, N. V. Structures of mitochondrial oxidative phosphorylation supercomplexes and mechanisms for their stabilisation. Biochim. Biophys. Acta. 1837, 418–426 (2014).

    CAS  PubMed  Google Scholar 

  135. 135.

    Lapuente-Brun, E. et al. Supercomplex assembly determines electron flux in the mitochondrial electron transport chain. Science 340, 1567–1570 (2013).

    CAS  Google Scholar 

  136. 136.

    Lukeš, J., Archibald, J. M., Keeling, P. J., Doolittle, W. F. & Gray, M. W. How a neutral evolutionary ratchet can build cellular complexity. IUBMB Life 63, 528–537 (2011).

    PubMed  Google Scholar 

  137. 137.

    Nishimura, K. & van Wijk, K. J. Organization, function and substrates of the essential Clp protease system in plastids. Biochim. Biophys. Acta. 1847, 915–930 (2015).

    CAS  PubMed  Google Scholar 

  138. 138.

    Sinkler, C. A. et al. Tissue-and condition-specific isoforms of mammalian cytochrome c oxidase subunits: from function to human disease. Oxidative Med. Cell. Longev. 2017, 1534056 (2017).

    Google Scholar 

  139. 139.

    Frank, S. A. & Hurst, L. D. Mitochondria and male disease. Nature 383, 224 (1996).

    CAS  PubMed  Google Scholar 

  140. 140.

    Gemmell, N. J., Metcalf, V. J. & Allendorf, F. W. Mother’s curse: the effect of mtDNA on individual fitness and population viability. Trends Ecol. Evol. 19, 238–244 (2004).

    PubMed  Google Scholar 

  141. 141.

    Gallach, M., Chandrasekaran, C. & Betran, E. Analyses of nuclearly encoded mitochondrial genes suggest gene duplication as a mechanism for resolving intralocus sexually antagonistic conflict in Drosophila. Genome Biol. Evol. 2, 835–850 (2010).

    PubMed  PubMed Central  Google Scholar 

  142. 142.

    Patel, M. R. et al. A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster. eLife 5, e16923 (2016).

    PubMed  PubMed Central  Google Scholar 

  143. 143.

    Small, I. et al. The strange evolutionary history of plant mitochondrial tRNAs and their aminoacyl-tRNA synthetases. J. Hered. 90, 333–337 (1999).

    CAS  Google Scholar 

  144. 144.

    Roger, A. J., Muñoz-Gómez, S. A. & Kamikawa, R. The origin and diversification of mitochondria. Curr. Biol. 27, R1177–R1192 (2017).

    CAS  PubMed  Google Scholar 

  145. 145.

    Daley, D. O. & Whelan, J. Why genes persist in organelle genomes. Genome Biol. 6, 110 (2005).

    PubMed  PubMed Central  Google Scholar 

  146. 146.

    Björkholm, P., Harish, A., Hagström, E., Ernst, A. M. & Andersson, S. G. Mitochondrial genomes are retained by selective constraints on protein targeting. Proc. Natl Acad. Sci. USA 112, 10154–10161 (2015).

    PubMed  Google Scholar 

  147. 147.

    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).

    CAS  PubMed  Google Scholar 

  148. 148.

    Oca-Cossio, J., Kenyon, L., Hao, H. & Moraes, C. T. Limitations of allotopic expression of mitochondrial genes in mammalian cells. Genetics 165, 707–720 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. 149.

    Allen, J. F. The function of genomes in bioenergetic organelles. Phil. Trans. R. Soc. Series B Biol. Sci. 358, 19–37 (2003).

    CAS  Google Scholar 

  150. 150.

    Allen, J. F. Why chloroplasts and mitochondria retain their own genomes and genetic systems: colocation for redox regulation of gene expression. Proc. Natl Acad. Sci. USA 112, 10231–10238 (2015). This review provides a recent summary of the classic co-location for redox regulation (CoRR) hypothesis for why mitochondria and plastids still retain their own genomes after billions of years of evolution.

    CAS  PubMed  Google Scholar 

  151. 151.

    Kanevski, I. & Maliga, P. Relocation of the plastid rbcL gene to the nucleus yields functional ribulose-1, 5-bisphosphate carboxylase in tobacco chloroplasts. Proc. Natl Acad. Sci. USA 91, 1969–1973 (1994).

    CAS  PubMed  Google Scholar 

  152. 152.

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

    CAS  Google Scholar 

  153. 153.

    Freibert, S.-A. et al. Evolutionary conservation and in vitro reconstitution of microsporidian iron–sulfur cluster biosynthesis. Nat. Communications 8, 13932 (2017).

    CAS  Google Scholar 

  154. 154.

    Karnkowska, A. et al. A eukaryote without a mitochondrial organelle. Curr. Biol. 26, 1274–1284 (2016).

    CAS  PubMed  Google Scholar 

  155. 155.

    Smith, D. R. & Lee, R. W. A plastid without a genome: evidence from the nonphotosynthetic green algal genus Polytomella. Plant Physiol. 164, 1812–1819 (2014).

    CAS  PubMed  Google Scholar 

  156. 156.

    Molina, J. et al. Possible loss of the chloroplast genome in the parasitic flowering plant Rafflesia lagascae (Rafflesiaceae). Mol. Biol. Evol. 31, 793–803 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. 157.

    Bennett, G. M. & Moran, N. A. Small, smaller, smallest: the origins and evolution of ancient dual-obligate symbioses in a phloem-feeding insect. Genome Biol. Evol. 5, 1675–1688 (2013).

    PubMed  PubMed Central  Google Scholar 

  158. 158.

    Sloan, D. B. et al. Parallel histories of horizontal gene transfer facilitated extreme reduction of endosymbiont genomes in sap-feeding insects. Mol. Biol. Evol. 31, 857–871 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. 159.

    Nowack, E. C. et al. Endosymbiotic gene transfer and transcriptional regulation of transferred genes in Paulinella chromatophora. Mol. Biol. Evol. 28, 407–422 (2011).

    CAS  PubMed  Google Scholar 

  160. 160.

    Singer, A. et al. Massive protein import into the early-evolutionary-stage photosynthetic organelle of the amoeba Paulinella chromatophora. Curr. Biol. 27, 2763–2773 (2017).

    CAS  PubMed  Google Scholar 

  161. 161.

    Nakabachi, A., Ishida, K., Hongoh, Y., Ohkuma, M. & Miyagishima, S. Y. Aphid gene of bacterial origin encodes a protein transported to an obligate endosymbiont. Curr. Biol. 24, R640–R641 (2014).

    CAS  PubMed  Google Scholar 

  162. 162.

    Nowack, E. C. M. et al. Gene transfers from diverse bacteria compensate for reductive genome evolution in the chromatophore of Paulinella chromatophora. Proc. Natl Acad. Sci. USA 113, 12214–12219 (2016).

    CAS  PubMed  Google Scholar 

  163. 163.

    Husnik, F. et al. Horizontal gene transfer from diverse bacteria to an insect genome enables a tripartite nested mealybug symbiosis. Cell 153, 1567–1578 (2013). This comparative genomic analysis reveals the role of HGT from multiple sources in the more recent establishment of obligate bacterial endosymbionts in sap-feeding insects.

    CAS  PubMed  Google Scholar 

  164. 164.

    Bennett, G. M. & Moran, N. A. Heritable symbiosis: The advantages and perils of an evolutionary rabbit hole. Proc. Natl Acad. Sci. USA 112, 10169–10176 (2015).

    CAS  PubMed  Google Scholar 

  165. 165.

    Husnik, F. & McCutcheon, J. P. Repeated replacement of an intrabacterial symbiont in the tripartite nested mealybug symbiosis. Proc. Natl Acad. Sci. USA 113, E5416–5424 (2016).

    CAS  PubMed  Google Scholar 

  166. 166.

    Ball, S. G. et al. Toward an understanding of the function of Chlamydiales in plastid endosymbiosis. Biochim. Biophys. Acta. 1847, 495–504 (2015).

    CAS  PubMed  Google Scholar 

  167. 167.

    Domman, D., Horn, M., Embley, T. M. & Williams, T. A. Plastid establishment did not require a chlamydial partner. Nat. Commun. 6, 6421 (2015).

    PubMed  PubMed Central  Google Scholar 

  168. 168.

    Larkum, A. W., Lockhart, P. J. & Howe, C. J. Shopping for plastids. Trends Plant Sci. 12, 189–195 (2007).

    CAS  PubMed  Google Scholar 

  169. 169.

    Ku, C. et al. Endosymbiotic gene transfer from prokaryotic pangenomes: inherited chimerism in eukaryotes. Proc. Natl Acad. Sci. USA 112, 10139–10146 (2015). The authors of this study argue that inferences of diverse phylogenetic donors in the establishment of endosymbionts and organelles are often overestimated because they fail to account for errors in phylogenetic reconstruction and for the history of HGT in bacteria that preceded endosymbiosis.

    CAS  PubMed  Google Scholar 

  170. 170.

    Kapust, N. et al. Failure to recover major events of gene flux in real biological data due to method misapplication. Genome Biol. Evol. 10, 1198–1209 (2018).

    PubMed  PubMed Central  Google Scholar 

Download references


The authors thank the reviewers for their insightful comments on an earlier version of this manuscript. This work was supported by a National Institutes of Health (NIH) postdoctoral Fellowship (F32 GM116361 to J.C.H.), a National Science Foundation (NSF) Graduate Research Fellowship (DGE-1321845 to A.M.W.), an NSF-funded GAUSSI Graduate Fellowship (DGE-1450032 to J.M.W.) and grants from NSF (MCB-1412260 and MCB-1733227 to D.B.S.), NIH (NIGMS R01 GM118046 to D.B.S.) and the U.S. Department of Agriculture (2015-67017-23143 to A.J.C.).

Reviewer information

Nature Reviews Genetics thanks D. M. Rand, T. A. Richards, D. R. Smith and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

Author information




All authors contributed to researching data for the article, discussion of content and reviewing and editing the manuscript for submission. D.B.S. was primarily responsible for writing the manuscript.

Corresponding author

Correspondence to Daniel B. Sloan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.



Organelles that were endosymbiotically derived from cyanobacteria and can differentiate into multiple functional types, the most well known of which is the chloroplast.

Endosymbiotic gene transfer

(EGT). The process by which genes are functionally transferred from cytoplasmic genomes to the nucleus (also known as intracellular gene transfer).

Last eukaryotic common ancestor

(LECA). The most recent common ancestor of all extant eukaryotes — an organism that is thought to have already acquired mitochondria and undergone substantial cytonuclear integration.


The translocase of the inner mitochondrial membrane (TIM) and the translocase of the outer mitochondrial membrane (TOM) mediate import of nuclear-encoded proteins into the mitochondria.


The translocase of the inner chloroplast membrane (TIC) and the translocase of the outer chloroplast membrane (TOC) mediate import of nuclear-encoded proteins into the plastids.

Nuclear mitochondrial DNAs

(NUMTs). Insertions of mitochondrial DNA into the nucleus (usually non-functional).

Nuclear plastid DNAs

(NUPTs). Insertions of plastid DNA into the nucleus (usually non-functional).

Double-stranded breaks

Breaks in DNA molecules that, when subsequently repaired by processes such as non-homologous end-joining, can result in incorporation of other DNA sequences.


The process by which a mature RNA transcript is reverse transcribed and recombined back into the genome.

Oxidative phosphorylation

(OXPHOS). A biochemical process that occurs in the mitochondria and is mediated by a set of cytonuclear enzyme complexes, in which energy generated by electron transfer results in the synthesis of ATP.

Supernumerary subunits

Protein subunits within cytonuclear enzyme complexes that were not present in the bacterial progenitors of mitochondria or plastids and have been recruited to these complexes during eukaryotic evolution.


Genes that are related to each other as the result of an earlier gene duplication event within a genome.

Mother’s curse

The concept articulated by Frank and Hurst and later named by Gemmell et al. that cytoplasmic alleles that are harmful to male reproduction may persist in populations because strict maternal inheritance shields these effects from selection.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sloan, D.B., Warren, J.M., Williams, A.M. et al. Cytonuclear integration and co-evolution. Nat Rev Genet 19, 635–648 (2018).

Download citation

Further reading