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.

  • Opinion
  • Published:

First among equals: competition between genetically identical cells

Nature Reviews Genetics volume 7, pages 577–583 (2006)Cite this article

Abstract

Competition between genetically identical organisms is considered insignificant in evolutionary theory because it is presumed to have little selective consequence. We argue that competition between genetically identical cells could improve the fitness of a multicellular organism by directing fitter cells to the germ line or by eliminating unfit cells, and that cell-competition mechanisms have been conserved in multicellular organisms. We propose that competition between genetically identical or highly similar units could have similar selective advantages at higher organizational levels, such as societies.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Lateral inhibition determines cell-type proportions.
Figure 2: Sweetness is rewarded.
Figure 3: Developmental asymmetry that is conferred by differential DNA strand segregation.

Similar content being viewed by others

References

  1. Hamilton, W. D. The genetical evolution of social behaviour. I. J. Theor. Biol. 7, 1–16 (1964).

    Article  CAS  PubMed  Google Scholar 

  2. Hamilton, W. D. The genetical evolution of social behaviour. II. J. Theor. Biol. 7, 17–52 (1964).

    Article  CAS  PubMed  Google Scholar 

  3. Maynard Smith, J. & Szathmary, E. The Major Transitions in Evolution (Oxford Univ. Press, New York, 1995).

    Google Scholar 

  4. Michod, R. Darwinian Dynamics (Princeton Univ. Press, Princeton, New Jersey, 1999).

    Google Scholar 

  5. Shaulsky, G. & Loomis, W. F. Cell type regulation in response to expression of ricin A in Dictyostelium. Dev. Biol. 160, 85–98 (1993).

    Article  CAS  PubMed  Google Scholar 

  6. Greenwald, I. LIN-12/Notch signaling: lessons from worms and flies. Genes Dev. 12, 1751–1762 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. Rooke, J. E. & Xu, T. Positive and negative signals between interacting cells for establishing neural fate. Bioessays 20, 209–214 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Lewis, J. Notch signalling and the control of cell fate choices in vertebrates. Semin. Cell Dev. Biol. 9, 583–589 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. Morata, G. & Ripoll, P. Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 42, 211–221 (1975).

    Article  CAS  PubMed  Google Scholar 

  10. Lambertsson, A. The minute genes in Drosophila and their molecular functions. Adv. Genet. 38, 69–134 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. Simpson, P. & Morata, G. Differential mitotic rates and patterns of growth in compartments in the Drosophila wing. Dev. Biol. 85, 299–308 (1981).

    Article  CAS  PubMed  Google Scholar 

  12. Prober, D. A. & Edgar, B. A. Ras1 promotes cellular growth in the Drosophila wing. Cell 100, 435–446 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. de la Cova, C., Abril, M., Bellosta, P., Gallant, P. & Johnston, L. A. Drosophila Myc regulates organ size by inducing cell competition. Cell 117, 107–116 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Moreno, E. & Basler, K. dMyc transforms cells into super-competitors. Cell 117, 117–129 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Burke, R. & Basler, K. Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. Development 122, 2261–2269 (1996).

    CAS  PubMed  Google Scholar 

  16. Johnston, L. A. & Sanders, A. L. Wingless promotes cell survival but constrains growth during Drosophila wing development. Nature Cell Biol. 5, 827–833 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Abrams, J. M. Competition and compensation: coupled to death in development and cancer. Cell 110, 403–406 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Milan, M. Survival of the fittest. Cell competition in the Drosophila wing. EMBO Rep. 3, 724–725 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Moreno, E., Basler, K. & Morata, G. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416, 755–759 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Oliver, E. R., Saunders, T. L., Tarle, S. A. & Glaser, T. Ribosomal protein L24 defect in belly spot and tail (Bst), a mouse Minute. Development 131, 3907–3920 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Gallardo, M. H., Bickham, J. W., Honeycutt, R. L., Ojeda, R. A. & Kohler, N. Discovery of tetraploidy in a mammal. Nature 401, 341 (1999).

    Article  CAS  PubMed  Google Scholar 

  22. Eakin, G. S. & Behringer, R. R. Tetraploid development in the mouse. Dev. Dyn. 228, 751–766 (2003).

    Article  PubMed  Google Scholar 

  23. Eakin, G. S., Hadjantonakis, A. K., Papaioannou, V. E. & Behringer, R. R. Developmental potential and behavior of tetraploid cells in the mouse embryo. Dev. Biol. 288, 150–159 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Heard, E., Clerc, P. & Avner, P. X-chromosome inactivation in mammals. Annu. Rev. Genet. 31, 571–610 (1997).

    Article  CAS  PubMed  Google Scholar 

  25. Migeon, B. R. Non-random X chromosome inactivation in mammalian cells. Cytogenet. Cell. Genet. 80, 142–148 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Van den Veyver, I. B. Skewed X inactivation in X-linked disorders. Semin. Reprod. Med. 19, 183–191 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Belmont, J. W. Genetic control of X inactivation and processes leading to X-inactivation skewing. Am. J. Hum. Genet. 58, 1101–1108 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Conley, M. E. et al. Expression of the gene defect in X-linked agammaglobulinemia. N. Engl. J. Med. 315, 564–567 (1986).

    Article  CAS  PubMed  Google Scholar 

  29. Fearon, E. R., Winkelstein, J. A., Civin, C. I., Pardoll, D. M. & Vogelstein, B. Carrier detection in X-linked agammaglobulinemia by analysis of X-chromosome inactivation. N. Engl. J. Med. 316, 427–431 (1987).

    Article  CAS  PubMed  Google Scholar 

  30. Puck, J. M., Nussbaum, R. L. & Conley, M. E. Carrier detection in X-linked severe combined immunodeficiency based on patterns of X chromosome inactivation. J. Clin. Invest. 79, 1395–1400 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fearon, E. R., Kohn, D. B., Winkelstein, J. A., Vogelstein, B. & Blaese, R. M. Carrier detection in the Wiskott Aldrich syndrome. Blood 72, 1735–1739 (1988).

    CAS  PubMed  Google Scholar 

  32. Greer, W. L. et al. X-chromosome inactivation in the Wiskott–Aldrich syndrome: a marker for detection of the carrier state and identification of cell lineages expressing the gene defect. Genomics 4, 60–67 (1989).

    Article  CAS  PubMed  Google Scholar 

  33. Parrish, J. E., Scheuerle, A. E., Lewis, R. A., Levy, M. L. & Nelson, D. L. Selection against mutant alleles in blood leukocytes is a consistent feature in incontinentia pigmenti type 2. Hum. Mol. Genet. 5, 1777–1783 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. Wengler, G., Gorlin, J. B., Williamson, J. M., Rosen, F. S. & Bing, D. H. Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott–Aldrich syndrome. Blood 85, 2471–2477 (1995).

    CAS  PubMed  Google Scholar 

  35. Parolini, O. et al. X-linked Wiskott–Aldrich syndrome in a girl. N. Engl. J. Med. 338, 291–295 (1998).

    Article  CAS  PubMed  Google Scholar 

  36. Ellermeier, C. D., Hobbs, E. C., Gonzalez-Pastor, J. E. & Losick, R. A three-protein signaling pathway governing immunity to a bacterial cannibalism toxin. Cell 124, 549–559 (2006).

    Article  CAS  PubMed  Google Scholar 

  37. Gonzalez-Pastor, J. E., Hobbs, E. C. & Losick, R. Cannibalism by sporulating bacteria. Science 301, 510–513 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Loomis, W. F. Dictyostelium discoideum. A Developmental System (Academic Press, New York, 1975).

    Google Scholar 

  39. Kessin, R. H. Dictyostelium — Evolution, Cell Biology, and the Development of Multicellularity (Cambridge Univ. Press, Cambridge, UK, 2001).

    Book  Google Scholar 

  40. Leach, C. K., Ashworth, J. M. & Garrod, D. R. Cell sorting out during the differentiation of mixtures of metabolically distinct populations of Dictyostelium discoideum. J. Embryol. Exp. Morphol. 29, 647–661 (1973).

    CAS  PubMed  Google Scholar 

  41. Tasaka, M. & Takeuchi, I. Role of cell sorting in pattern formation in Dictyostelium discoideum. Differentiation 18, 191–196 (1981).

    Article  CAS  PubMed  Google Scholar 

  42. Thompson, C. R. & Kay, R. R. Cell-fate choice in Dictyostelium: intrinsic biases modulate sensitivity to DIF signaling. Dev. Biol. 227, 56–64 (2000).

    Article  CAS  PubMed  Google Scholar 

  43. Blaschke, A., Weijer, C. & MacWilliams, H. Dictyostelium discoideum: Cell-type proportioning, cell-differentiation preference, cell fate, and the behavior of anterior-like cells in Hs1/Hs2 and G+/G− mixtures. Differentiation 32, 1–9 (1986).

    Article  Google Scholar 

  44. McDonald, S. A. & Durston, A. J. The cell cycle and sorting behaviour in Dictyostelium discoideum. J. Cell Sci. 66, 195–204 (1984).

    CAS  PubMed  Google Scholar 

  45. Araki, T., Nakao, H., Takeuchi, I. & Maeda, Y. Cell-cycle-dependent sorting in the development of Dictyostelium cells. Dev. Biol. 162, 221–228 (1994).

    Article  CAS  PubMed  Google Scholar 

  46. Weijer, C. J., Duschl, G. & David, C. N. Dependence of cell-type proportioning and sorting on cell cycle phase in Dictyostelium discoideum. J. Cell Sci. 70, 133–145 (1984).

    CAS  PubMed  Google Scholar 

  47. Strassmann, J. E., Zhu, Y. & Queller, D. C. Altruism and social cheating in the social amoeba Dictyostelium discoideum. Nature 408, 965–967 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. Laird, D. J., De Tomaso, A. W. & Weissman, I. L. Stem cells are units of natural selection in a colonial ascidian. Cell 123, 1351–1360 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. De Tomaso, A. W. et al. Isolation and characterization of a protochordate histocompatibility locus. Nature 438, 454–459 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Stoner, D. S. & Weissman, I. L. Somatic and germ cell parasitism in a colonial ascidian: possible role for a highly polymorphic allorecognition system. Proc. Natl Acad. Sci. USA 93, 15254–15259 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Stoner, D. S., Rinkevich, B. & Weissman, I. L. Heritable germ and somatic cell lineage competitions in chimeric colonial protochordates. Proc. Natl Acad. Sci. USA 96, 9148–9153 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Extavour, C. G. & Akam, M. Mechanisms of germ cell specification across the metazoans: epigenesis and preformation. Development 130, 5869–5884 (2003).

    Article  CAS  PubMed  Google Scholar 

  53. Buss, L. W. Evolution, development, and the units of selection. Proc. Natl Acad. Sci. USA 80, 1387–1391 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Johnson, J. et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 122, 303–315 (2005).

    Article  CAS  PubMed  Google Scholar 

  55. Miyata, H. & Miyata, M. Mode of conjugation in homothallic cells of Schizosaccharomyces pombe. J. Gen. Appl. Microbiol. 27, 365–371 (1981).

    Article  Google Scholar 

  56. Klar, A. J. Differentiated parental DNA strands confer developmental asymmetry on daughter cells in fission yeast. Nature 326, 466–470 (1987).

    Article  CAS  PubMed  Google Scholar 

  57. Klar, A. J. The developmental fate of fission yeast cells is determined by the pattern of inheritance of parental and grandparental DNA strands. EMBO J. 9, 1407–1415 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lark, K. G. Nonrandom segregation of sister chromatids in Vicia faba and Triticum boeoticum. Proc. Natl Acad. Sci. USA 58, 352–359 (1967).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Rosenberger, R. F. & Kessel, M. Nonrandom sister chromatid segregation and nuclear migration in hyphae of Aspergillus nidulans. J. Bacteriol. 96, 1208–1213 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Lark, K. G., Consigli, R. A. & Minocha, H. C. Segregation of sister chromatids in mammalian cells. Science 154, 1202–1205 (1966).

    Article  CAS  PubMed  Google Scholar 

  61. Potten, C. S., Hume, W. J., Reid, P. & Cairns, J. The segregation of DNA in epithelial stem cells. Cell 15, 899–906 (1978).

    Article  CAS  PubMed  Google Scholar 

  62. Potten, C. S., Owen, G. & Booth, D. Intestinal stem cells protect their genome by selective segregation of template DNA strands. J. Cell Sci. 115, 2381–2388 (2002).

    CAS  PubMed  Google Scholar 

  63. Merok, J. R., Lansita, J. A., Tunstead, J. R. & Sherley, J. L. Cosegregation of chromosomes containing immortal DNA strands in cells that cycle with asymmetric stem cell kinetics. Cancer Res. 62, 6791–6795 (2002).

    CAS  PubMed  Google Scholar 

  64. Karpowicz, P. et al. Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro. J. Cell Biol. 170, 721–732 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kaykov, A. & Arcangioli, B. A programmed strand-specific and modified nick in S. pombe constitutes a novel type of chromosomal imprint. Curr. Biol. 14, 1924–1928 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Vengrova, S. & Dalgaard, J. Z. RNase-sensitive DNA modification(s) initiates S. pombe mating-type switching. Genes Dev. 18, 794–804 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197–200 (1975).

    Article  CAS  PubMed  Google Scholar 

  68. Armakolas, A. & Klar, A. J. Cell type regulates selective segregation of mouse chromosome 7 DNA strands in mitosis. Science 311, 1146–1149 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Frank, S. A. Mutual policing and repression of competition in the evolution of cooperative groups. Nature 377, 520–522 (1995).

    Article  CAS  PubMed  Google Scholar 

  70. Jacob, F. Evolution and tinkering. Science 196, 1161–1166 (1977).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank D. Queller, L. Santorelli, A. Kuspa and B. Loomis for critical review of this manuscript and for helpful discussions. We thank Z. Pancer, J. Strassmann and N. Boerkoel for enlightening discussions. This work has been supported by a FIBR (Frontiers in Integrative Biological Research) grant from the US National Science Foundation.

Author information

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, USA

    Anupama Khare & Gad Shaulsky

Authors
  1. Anupama Khare
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gad Shaulsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gad Shaulsky.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

OMIM

incontinentia pigmenti type 2

Wiskott–Aldrich syndrome

X-linked agammaglobulinaemia

X-linked severe combined immunodeficiency

FURTHER INFORMATION

Gad Shaulsky's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khare, A., Shaulsky, G. First among equals: competition between genetically identical cells. Nat Rev Genet 7, 577–583 (2006). https://doi.org/10.1038/nrg1875

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg1875

This article is cited by

Search

Advanced 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