Gene amplification as a form of population-level gene expression regulation


Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature.

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Fig. 1: An experimental system for monitoring gene copy number under fluctuating selection in real time.
Fig. 2: AMGET occurs in fluctuating environments.
Fig. 3: High-frequency deletion and duplication events in the amplified locus create gene-copy-number polymorphisms in populations.
Fig. 4: AMGET requires continual generation of gene-copy-number polymorphisms.
Fig. 5: AMGET is a robust strategy for tuning population-level gene expression across a range of environments.

Data availability

Experimental data that support the findings of this study have been deposited in IST DataRep and are publicly available at

Code availability

The scripts for our mathematical model and for the analysis of microfluidics time traces have been deposited in IST DataRep and are publicly available at


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We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences.

Author information

C.C.G., R.G., M.L., G.T. and I.T. conceived the study. I.T. performed experiments. A.M.C.A., R.G. and I.T. analysed data. R.G. and G.T. performed the formal analysis. R.G. and I.T. wrote the original draft and revised with A.M.C.A., J.P.B., C.C.G., M.L. and G.T.

Correspondence to C. C. Guet.

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Supplementary Information

Supplementary note, Figs. 1–7, Tables 2, 4 and 5, and references.

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Supplementary Tables

Supplementary Table 1: verification of amplification events by detailed analysis of time-lapse microscopy images. Supplementary Table 3: a list of oligonucleotides.

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Tomanek, I., Grah, R., Lagator, M. et al. Gene amplification as a form of population-level gene expression regulation. Nat Ecol Evol (2020).

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