Skip to main content

Advertisement

Log in

Self-organization vs Watchmaker: stochastic gene expression and cell differentiation

  • Hypothesis Paper
  • Published:
Development Genes and Evolution Aims and scope Submit manuscript

Abstract

Cell differentiation and organism development are traditionally described in deterministic terms of program and design, echoing a conventional clockwork perception of the cell on another scale. However, the current experimental reality of stochastic gene expression and cell plasticity is poorly consistent with the ideas of design, purpose and determinism, suggesting that the habit of classico-mechanistic interpretation of life phenomena may handicap our ability to adequately comprehend and model biological systems. An alternative conceptualization of cell differentiation and development is proposed where the developing organism is viewed as a dynamic self-organizing system of adaptive interacting agents. This alternative interpretation appears to be more consistent with the probabilistic nature of gene expression and the phenomena of cell plasticity, and is coterminous with the novel emerging image of the cell as a self-organizing molecular system. I suggest that stochasticity, as a principle of differentiation and adaptation, and self-organization, as a concept of emergence, have the potential to provide an interpretational framework that unites phenomena across different scales of biological organization, from molecules to societies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA (2000) Hepatocytes from non-hepatic adult stem cells. Nature 406:257

    Article  CAS  PubMed  Google Scholar 

  • Beshers SN, Fewell JH (2001) Models of division of labor in social insects. Annu Rev Entomol 46:413–440

    Article  CAS  PubMed  Google Scholar 

  • Biggar SR, Crabtree GR (2001) Cell signaling can direct either binary or graded transcriptional responses. EMBO J 20:3167–3176

    Article  CAS  PubMed  Google Scholar 

  • Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283:534–537

    Article  CAS  PubMed  Google Scholar 

  • Blake WJ, M KA, Cantor CR, Collins JJ (2003) Noise in eukaryotic gene expression. Nature 422:633–637

    Article  CAS  PubMed  Google Scholar 

  • Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290:1775–1779

    Article  CAS  PubMed  Google Scholar 

  • Chelly J, Concordet JP, Kaplan JC, Kahn A (1989) Illegitimate transcription: transcription of any gene in any cell type. Proc Natl Acad Sci USA 86:2617–2621

    CAS  PubMed  Google Scholar 

  • Cheutin T, Gorski SA, May KM, Singh PB, Misteli T (2004) In vivo dynamics of Swi6 in yeast: evidence for a stochastic model of heterochromatin. Mol Cell Biol 24:3157–3167

    Article  CAS  PubMed  Google Scholar 

  • Cook DL, Gerber AN, Tapscott SJ (1998) Modeling stochastic gene expression: implications for haploinsufficiency. Proc Natl Acad Sci USA 95:15641–15646

    Article  CAS  PubMed  Google Scholar 

  • Dundr M, Hoffmann-Rohrer U, Hu Q, Grummt I, Rothblum LI, Phair RD, Misteli T (2002) A kinetic framework for a mammalian RNA polymerase in vivo. Science 298:1623–1626

    Article  CAS  PubMed  Google Scholar 

  • Essers J, Houtsmuller AB, van Veelen L, Paulusma C, Nigg AL, Pastink A, Vermeulen W, Hoeijmakers JH, Kanaar R (2002) Nuclear dynamics of RAD52 group homologous recombination proteins in response to DNA damage. EMBO J 21:2030–2037

    Article  CAS  PubMed  Google Scholar 

  • Femino AM, Fay FS, Fogarty K, Singer RH (1998) Visualization of single RNA transcripts in situ. Science 280:585–590

    Article  CAS  PubMed  Google Scholar 

  • Fewell JH (2003) Social insect networks. Science 301:1867–1870

    Article  CAS  PubMed  Google Scholar 

  • Fiering S, Northrop JP, Nolan GP, Mattila PS, Crabtree GR, Herzenberg LA (1990) Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor. Genes Dev 4:1823–1834

    CAS  PubMed  Google Scholar 

  • Fiering S, Whitelaw E, Martin DI (2000) To be or not to be active: the stochastic nature of enhancer action. Bioessays 22:381–387

    PubMed  Google Scholar 

  • Grande MA, van der Kraan I, de Jong L, van Driel R (1997) Nuclear distribution of transcription factors in relation to sites of transcription and RNA polymerase II. J Cell Sci 110(15):1781–1791

    PubMed  Google Scholar 

  • Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS (2004) Lack of a fusion requirement for development of bone marrow-derived epithelia. Science 305:90–93

    Article  CAS  PubMed  Google Scholar 

  • Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, Paupard MC, Hall DH, Driscoll M (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419:808–814

    Article  CAS  PubMed  Google Scholar 

  • Ho SN, Biggar SR, Spencer DM, Schreiber SL, Crabtree GR (1996) Dimeric ligands define a role for transcriptional activation domains in reinitiation. Nature 382:822–826

    Article  CAS  PubMed  Google Scholar 

  • Hoogstraten D, Nigg AL, Heath H, Mullenders LH, van Driel R, Hoeijmakers JH, Vermeulen W, Houtsmuller AB (2002) Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo. Mol Cell 10:1163–1174

    Article  CAS  PubMed  Google Scholar 

  • Hume DA (2000) Probability in transcriptional regulation and its implications for leukocyte differentiation and inducible gene expression. Blood 96:2323–2328

    CAS  PubMed  Google Scholar 

  • Iborra FJ, Pombo A, Jackson DA, Cook PR (1996) Active RNA polymerases are localized within discrete transcription “factories’ in human nuclei. J Cell Sci 109(6):1427–1436

    CAS  PubMed  Google Scholar 

  • Jouvenot Y, Poirier F, Jami J, Paldi A (1999) Biallelic transcription of Igf2 and H19 in individual cells suggests a post-transcriptional contribution to genomic imprinting. Curr Biol 9:1199–1202

    Article  CAS  PubMed  Google Scholar 

  • Kimura H, Sugaya K, Cook PR (2002) The transcription cycle of RNA polymerase II in living cells. J Cell Biol 159:777–782

    Article  CAS  PubMed  Google Scholar 

  • Ko MS, Nakauchi H, Takahashi N (1990) The dose dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates. EMBO J 9:2835–2842

    CAS  PubMed  Google Scholar 

  • Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369–377

    Article  Google Scholar 

  • Kringstein AM, Rossi FM, Hofmann A, Blau HM (1998) Graded transcriptional response to different concentrations of a single transactivator. Proc Natl Acad Sci USA 95:13670–13675

    Article  CAS  PubMed  Google Scholar 

  • Kupiec JJ (1997) A Darwinian theory for the origin of cellular differentiation. Mol Gen Genet 255:201–208

    Article  CAS  PubMed  Google Scholar 

  • Kurakin A (2004) Self-organization versus Watchmaker: stochasticity and determinism in molecular and cell biology. Available at http://www.alexeikurakin.org/text/ak030304.pdf

  • Kuznetsov VA, Knott GD, Bonner RF (2002) General statistics of stochastic process of gene expression in eukaryotic cells. Genetics 161:1321–1332

    CAS  PubMed  Google Scholar 

  • Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229–1234

    Article  CAS  PubMed  Google Scholar 

  • Levsky JM, Shenoy SM, Pezo RC, Singer RH (2002) Single-cell gene expression profiling. Science 297:836–840

    Article  CAS  PubMed  Google Scholar 

  • Li L, Connelly MC, Wetmore C, Curran T, Morgan JI (2003) Mouse embryos cloned from brain tumors. Cancer Res 63:2733–2736

    CAS  PubMed  Google Scholar 

  • Loeffler M, Roeder I (2002) Tissue stem cells: definition, plasticity, heterogeneity, self-organization and models—a conceptual approach. Cells Tissues Organs 171:8–26

    Article  PubMed  Google Scholar 

  • Misteli T (2001) The concept of self-organization in cellular architecture. J Cell Biol 155:181–185

    Article  CAS  PubMed  Google Scholar 

  • Misteli T, Gunjan A, Hock R, Bustin M, Brown DT (2000) Dynamic binding of histone H1 to chromatin in living cells. Nature 408:877–881

    Article  CAS  PubMed  Google Scholar 

  • Morel B, Ramanujam R (1999) Through the looking glass of complexity: the dynamics of organizations as adaptive and evolving systems. Organ Sci 10:278–293

    Google Scholar 

  • Nedelec F, Surrey T, Karsenti E (2003) Self-organisation and forces in the microtubule cytoskeleton. Curr Opin Cell Biol 15:118–124

    Article  CAS  PubMed  Google Scholar 

  • Newlands S, Levitt LK, Robinson CS, Karpf AB, Hodgson VR, Wade RP, Hardeman EC (1998) Transcription occurs in pulses in muscle fibers. Genes Dev 12:2748–2758

    CAS  PubMed  Google Scholar 

  • Ogawa M (1993) Differentiation and proliferation of hematopoietic stem cells. Blood 81:2844–2853

    CAS  PubMed  Google Scholar 

  • Paldi A (2003) Stochastic gene expression during cell differentiation: order from disorder? Cell Mol Life Sci 60:1775–1778

    Article  CAS  PubMed  Google Scholar 

  • Roeder I, Loeffler M (2002) A novel dynamic model of hematopoietic stem cell organization based on the concept of within-tissue plasticity. Exp Hematol 30:853–861

    Article  CAS  PubMed  Google Scholar 

  • Ross IL, Browne CM, Hume DA (1994) Transcription of individual genes in eukaryotic cells occurs randomly and infrequently. Immunol Cell Biol 72:177–185

    CAS  PubMed  Google Scholar 

  • Rossi FM, Kringstein AM, Spicher A, Guicherit OM, Blau HM (2000) Transcriptional control: rheostat converted to on/off switch. Mol Cell 6:723–728

    Article  CAS  PubMed  Google Scholar 

  • Sandaltzopoulos R, Becker PB (1998) Heat shock factor increases the reinitiation rate from potentiated chromatin templates. Mol Cell Biol 18:361–367

    CAS  PubMed  Google Scholar 

  • Sasai M, Wolynes PG (2003) Stochastic gene expression as a many-body problem. Proc Natl Acad Sci USA 100:2374–2379

    Article  CAS  PubMed  Google Scholar 

  • Serizawa S, Miyamichi K, Nakatani H, Suzuki M, Saito M, Yoshihara Y, Sakano H (2003) Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse. Science 302:2088–2094

    Article  CAS  PubMed  Google Scholar 

  • Takasuka N, White MR, Wood CD, Robertson WR, Davis JR (1998) Dynamic changes in prolactin promoter activation in individual living lactotrophic cells. Endocrinology 139:1361–1368

    Article  CAS  PubMed  Google Scholar 

  • Thattai M, van Oudenaarden A (2001) Intrinsic noise in gene regulatory networks. Proc Natl Acad Sci USA 98:8614–8619

    Article  CAS  PubMed  Google Scholar 

  • Theise ND, Krause DS (2002) Toward a new paradigm of cell plasticity. Leukemia 16:542–548

    Article  CAS  PubMed  Google Scholar 

  • Theise ND, Wilmut I (2003) Cell plasticity: flexible arrangement. Nature 425:21

    Article  CAS  PubMed  Google Scholar 

  • Tian XC (2004) Reprogramming of epigenetic inheritance by somatic cell nuclear transfer. Reprod Biomed Online 8:501–508

    PubMed  Google Scholar 

  • Turcotte DL, Rundle JB (2002) Self-organized complexity in the physical, biological, and social sciences. Proc Natl Acad Sci USA 99(Suppl 1):2463–2465

    Article  PubMed  Google Scholar 

  • Vendruscolo M, Zurdo J, MacPhee CE, Dobson CM (2003) Protein folding and misfolding: a paradigm of self-assembly and regulation in complex biological systems. Philos Trans Ser A Math Phys Eng Sci 361:1205–1222

    Article  CAS  Google Scholar 

  • Walters MC, Fiering S, Eidemiller J, Magis W, Groudine M, Martin DI (1995) Enhancers increase the probability but not the level of gene expression. Proc Natl Acad Sci USA 92:7125–7129

    CAS  PubMed  Google Scholar 

  • Weintraub H (1988) Formation of stable transcription complexes as assayed by analysis of individual templates. Proc Natl Acad Sci USA 85:5819–5823

    CAS  PubMed  Google Scholar 

  • White MR, Masuko M, Amet L, Elliott G, Braddock M, Kingsman AJ, Kingsman SM (1995) Real-time analysis of the transcriptional regulation of HIV and hCMV promoters in single mammalian cells. J Cell Sci 108(2):441–455

    CAS  PubMed  Google Scholar 

  • Wurmser AE, Nakashima K, Summers RG, Toni N, D’Amour KA, Lie DC, Gage FH (2004) Cell fusion-independent differentiation of neural stem cells to the endothelial lineage. Nature 430:350–356

    Article  CAS  PubMed  Google Scholar 

  • Xie XS, Lu HP (1999) Single-molecule enzymology. J Biol Chem 274:15967–15970

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I express apologies to the authors whose works have not been cited due to space limitations. I thank Tom Misteli for critical reading of the manuscript and for his valuable suggestions. I thank Dale Bredesen, my friends and colleagues at the Buck Institute for their continuing support and for providing a stimulating environment.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexei Kurakin.

Additional information

Edited by R.J. Sommer

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kurakin, A. Self-organization vs Watchmaker: stochastic gene expression and cell differentiation. Dev Genes Evol 215, 46–52 (2005). https://doi.org/10.1007/s00427-004-0448-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00427-004-0448-7

Keywords

Navigation