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Evolvability and hierarchy in rewired bacterial gene networks


Sequencing DNA from several organisms has revealed that duplication and drift of existing genes have primarily moulded the contents of a given genome. Though the effect of knocking out or overexpressing a particular gene has been studied in many organisms, no study has systematically explored the effect of adding new links in a biological network. To explore network evolvability, we constructed 598 recombinations of promoters (including regulatory regions) with different transcription or σ-factor genes in Escherichia coli, added over a wild-type genetic background. Here we show that 95% of new networks are tolerated by the bacteria, that very few alter growth, and that expression level correlates with factor position in the wild-type network hierarchy. Most importantly, we find that certain networks consistently survive over the wild type under various selection pressures. Therefore new links in the network are rarely a barrier for evolution and can even confer a fitness advantage.

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Figure 1: Promoter–ORF network rewiring.
Figure 2: GFP expression and growth signatures of promoter–ORF recombinants.
Figure 3: Selection experiments.

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Microarray data are MIAME-compliant and have been deposited at ArrayExpress, accession E-MEXP-732.


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We thank A. Martinez Arias, J. Sharpe, M. Babu, P. Bork and B. Schoenwetter for critical reading of the manuscript; P. Ribeca for RegulonDB analysis; and B. Di Ventura and S. Martinez de Pablo for cloning assistance. C.H. and E.R. were funded by European Commission FP6 Netsensor Grant 012948.

Author Contributions M.I., C.L., K.M., P.B., C.H. and M.G.-C. carried out experiments. E.R. and C.L. did computational analysis. M.I., C.L. and L.S. conceived experiments. M.I. and L.S. supervised experiments.

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Correspondence to Mark Isalan.

Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-9 with Legends, Supplementary Methods and Supplementary Notes. (PDF 2727 kb)

Supplementary Data 1

The file contains Supplementary Data 1 with data for growth and GFP under 5 conditions. (XLS 242 kb)

Supplementary Data 2

The file contains Supplementary Data 2 with data for RTqPCR and raw growth signatures. (XLS 12012 kb)

Supplementary Data 3

The file contains Supplementary Data 3 with data for DNA chip analysis. (XLS 18086 kb)

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Isalan, M., Lemerle, C., Michalodimitrakis, K. et al. Evolvability and hierarchy in rewired bacterial gene networks. Nature 452, 840–845 (2008).

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