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Partial penetrance facilitates developmental evolution in bacteria

Nature volume 460, pages 510514 (23 July 2009) | Download Citation

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Development normally occurs similarly in all individuals within an isogenic population, but mutations often affect the fates of individual organisms differently1,2,3,4. This phenomenon, known as partial penetrance, has been observed in diverse developmental systems. However, it remains unclear how the underlying genetic network specifies the set of possible alternative fates and how the relative frequencies of these fates evolve5,6,7,8. Here we identify a stochastic cell fate determination process that operates in Bacillus subtilis sporulation mutants and show how it allows genetic control of the penetrance of multiple fates. Mutations in an intercompartmental signalling process generate a set of discrete alternative fates not observed in wild-type cells, including rare formation of two viable ‘twin’ spores, rather than one within a single cell. By genetically modulating chromosome replication and septation, we can systematically tune the penetrance of each mutant fate. Furthermore, signalling and replication perturbations synergize to significantly increase the penetrance of twin sporulation. These results suggest a potential pathway for developmental evolution between monosporulation and twin sporulation through states of intermediate twin penetrance. Furthermore, time-lapse microscopy of twin sporulation in wild-type Clostridium oceanicum shows a strong resemblance to twin sporulation in these B. subtilis mutants9,10. Together the results suggest that noise can facilitate developmental evolution by enabling the initial expression of discrete morphological traits at low penetrance, and allowing their stabilization by gradual adjustment of genetic parameters.

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Change history

  • 23 July 2009

    The spelling of O.C.L's name was corrected on 23 July 2009.


  1. 1.

    & Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. Genetics 96, 435–454 (1980)

  2. 2.

    , & Hsp90 as a capacitor of phenotypic variation. Nature 417, 618–624 (2002)

  3. 3.

    et al. HSP90 affects the expression of genetic variation and developmental stability in quantitative traits. Proc. Natl Acad. Sci. USA 105, 2963–2968 (2008)

  4. 4.

    Sporulation in Bacillus subtilis. Characterization of oligosporogenous mutants and comparison of their phenotypes with those of asporogenous mutants. J. Gen. Microbiol. 71, 1–15 (1972)

  5. 5.

    & Quantitative epigenetics. Nature Genet. 33, 6–8 (2003)

  6. 6.

    & Robustness and evolution: concepts, insights and challenges from a developmental model system. Heredity 100, 132–140 (2008)

  7. 7.

    Developmental plasticity and the origin of species differences. Proc. Natl Acad. Sci. USA 102 (suppl. 1). 6543–6549 (2005)

  8. 8.

    & The Plausibility of Life: Resolving Darwin’s Dilemma 71–108 (Yale Univ. Press, 2005)

  9. 9.

    Clostridium oceanicum, sp. n., a sporeforming anaerobe isolated from marine sediments. J. Bacteriol. 103, 811–813 (1970)

  10. 10.

    Alternatives to binary fission in bacteria. Nature Rev. Microbiol. 3, 214–224 (2005)

  11. 11.

    & Compartmentalization of gene expression during Bacillus subtilis spore formation. Microbiol. Mol. Biol. Rev. 68, 234–262 (2004)

  12. 12.

    , , & The chromosomal location of the Bacillus subtilis sporulation gene spoIIR is important for its function. J. Bacteriol. 182, 4425–4429 (2000)

  13. 13.

    , & Chromosomal organization governs the timing of cell type-specific gene expression required for spore formation in Bacillus subtilis. Mol. Microbiol. 39, 1471–1481 (2001)

  14. 14.

    & Genetic aspects of bacterial endospore formation. Bacteriol. Rev. 40, 908–962 (1976)

  15. 15.

    , & Identification of a gene, spoIIR, that links the activation of sigma E to the transcriptional activity of sigma F during sporulation in Bacillus subtilis. Proc. Natl Acad. Sci. USA 92, 2012–2016 (1995)

  16. 16.

    , & A three-protein inhibitor of polar septation during sporulation in Bacillus subtilis. Mol. Microbiol. 42, 1147–1162 (2001)

  17. 17.

    et al. A vital stain for studying membrane dynamics in bacteria: a novel mechanism controlling septation during Bacillus subtilis sporulation. Mol. Microbiol. 31, 1149–1159 (1999)

  18. 18.

    & Developmental commitment in a bacterium. Cell 121, 401–409 (2005)

  19. 19.

    , & A comparative genomic view of clostridial sporulation and physiology. Nature Rev. Microbiol. 3, 969–978 (2005)

  20. 20.

    & Propagation by sporulation in the guinea pig symbiont Metabacterium polyspora. Proc. Natl Acad. Sci. USA 95, 10218–10223 (1998)

  21. 21.

    & Does RNA polymerase help drive chromosome segregation in bacteria? Proc. Natl Acad. Sci. USA 99, 14089–14094 (2002)

  22. 22.

    , , & Effects of the chromosome partitioning protein Spo0J (ParB) on oriC positioning and replication initiation in Bacillus subtilis. J. Bacteriol. 185, 1326–1337 (2003)

  23. 23.

    & Asymmetric cell division in B. subtilis involves a spiral-like intermediate of the cytokinetic protein FtsZ. Cell 109, 257–266 (2002)

  24. 24.

    et al. Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis. Proc. Natl Acad. Sci. USA 103, 2368–2373 (2006)

  25. 25.

    , & Emended descriptions of Clostridium acetobutylicum and Clostridium beijerinckii, and descriptions of Clostridium saccharoperbutylacetonicum sp. nov. and Clostridium saccharobutylicum sp. nov. Int. J. Syst. Evol. Microbiol. 51, 2095–2103 (2001)

  26. 26.

    Canalization of development and the inheritance of acquired characters. Nature 150, 563–565 (1942)

  27. 27.

    , & The Hsp90 capacitor, developmental remodeling, and evolution: the robustness of gene networks and the curious evolvability of metamorphosis. Crit. Rev. Biochem. Mol. Biol. 42, 355–372 (2007)

  28. 28.

    , & Construction of a cloning site near one end of Tn917 into which foreign DNA may be inserted without affecting transposition in Bacillus subtilis or expression of the transposon-borne erm gene. Plasmid 12, 1–9 (1984)

  29. 29.

    & Molecular Biological Methods for Bacillus (Wiley, 1990)

  30. 30.

    , , , & Gene regulation at the single-cell level. Science 307, 1962–1965 (2005)

  31. 31.

    , , & An excitable gene regulatory circuit induces transient cellular differentiation. Nature 440, 545–550 (2006)

  32. 32.

    , , , & Tunability and noise dependence in differentiation dynamics. Science 315, 1716–1719 (2007)

  33. 33.

    & Cell-specific SpoIIIE assembly and DNA translocation polarity are dictated by chromosome orientation. Mol. Microbiol. 66, 1066–1079 (2007)

  34. 34.

    et al. The origins of 168, W23, and other Bacillus subtilis legacy strains. J. Bacteriol. 190, 6983–6995 (2008)

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We thank J. Leadbetter and E. Matson for their help with the anaerobic species. We thank R. Losick, A. Grossman, M. Fujita and A. Arkin for strains and advice. We thank R. Kishony, D. Jones, Wolfgang Schwarz, G. Suel, J.-G. Ojalvo, B. Shraiman, J. Levine, J. C. W. Locke, D. Sprinzak, L. Cai and other members of M.B.E. and P.J.P. labs for helpful discussions. Work in the P.J.P.’s lab was supported by Public Health Service Grant GM43577 from the US National Institutes of Health (NIH). Work in M.B.E.’s lab was supported by NIH grants R01GM079771 and P50 GM068763, US National Science Foundation CAREER Award 0644463 and the Packard Foundation. A.E. was supported by the International Human Frontier Science Organization and the European Molecular Biology Organization.

Author Contributions A.E., V.K.C., J.D., P.J.P. and M.B.E. designed the research; A.E., V.K.C., P.X., M.E.F. and O.C.L. performed the experiments; A.E. and V.K.C. analysed the results; and A.E. and M.B.E. wrote the paper.

Author information

Author notes

    • Avigdor Eldar
    •  & Vasant K. Chary

    These authors contributed equally to this work.


  1. Howard Hughes Medical Institute and Division of Biology and Department of Applied Physics, California Institute of Technology, Pasadena, California 91125, USA

    • Avigdor Eldar
    • , Michelle E. Fontes
    • , Oliver C. Losón
    •  & Michael B. Elowitz
  2. Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, Pennsylvania 19140, USA

    • Vasant K. Chary
    • , Panagiotis Xenopoulos
    •  & Patrick J. Piggot
  3. Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA

    • Jonathan Dworkin


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Corresponding author

Correspondence to Michael B. Elowitz.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Methods, Supplementary Figures S1-S13 with Legends, Supplementary References and Supplementary Legends for Movies 1 and 2.


  1. 1.

    Supplementary Movie 1

    This movie shows the partial penetrance of a spoIIRdelay microcolony growing and sporulating (strain AES528) - see file s1 for full legend.

  2. 2.

    Supplementary Movie 2

    This movie shows C. oceanicum sporulation - see file s1 for full legend.

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