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Partial penetrance facilitates developmental evolution in bacteria

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Abstract

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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Figure 1: Partial penetrance in the developmental process of sporulation.
Figure 2: Time-lapse movies reveal alternative developmental pathways in spoIIR PP signalling mutants.
Figure 3: Noise and gene expression control cell fate in a hierarchical fashion.
Figure 4: Evolution of twin sporulation.

Change history

  • 23 July 2009

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

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Acknowledgements

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.

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Correspondence to Michael B. Elowitz.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Figures S1-S13 with Legends, Supplementary References and Supplementary Legends for Movies 1 and 2. (PDF 2964 kb)

Supplementary Movie 1

This movie shows the partial penetrance of a spoIIRdelay microcolony growing and sporulating (strain AES528) - see file s1 for full legend. (MOV 7674 kb)

Supplementary Movie 2

This movie shows C. oceanicum sporulation - see file s1 for full legend. (MOV 10286 kb)

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Eldar, A., Chary, V., Xenopoulos, P. et al. Partial penetrance facilitates developmental evolution in bacteria. Nature 460, 510–514 (2009). https://doi.org/10.1038/nature08150

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