Adaptation dynamics between copy-number and point mutations

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Abstract

Together, copy-number and point mutations form the basis for most evolutionary novelty, through the process of gene duplication and divergence. While a plethora of genomic data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic reporter system that can distinguish between copy-number and point mutations, we study their early and transient adaptive dynamics in real-time in Escherichia coli. We find two qualitatively different routes of adaptation, depending on the level of functional improvement needed. In conditions of high gene expression demand, the two mutation types occur as a combination. However, under low gene expression demand, copy-number and point mutations are mutually exclusive; here, owing to their higher frequency, adaptation is dominated by copy-number mutations, in a process we term Amplification Hindrance. Ultimately, due to high reversal rates and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation, but also constrain sequence divergence over evolutionary time scales.

Data availability

Source Data and R scripts to generate the plots shown in the Figures are uploaded as the respective source code files.Flow cytometry and Illumina sequencing data are uploaded on Dryad together with R scripts to generate the plots shown in the respective Figures (Flow cytometry data: Figure 2C, 3C-D (and Figure Supplements), 4A; Illumina sequencing data: Figure 5 and (Figure Supplement)).

The following data sets were generated

1. Tomanek I
2. Guet C
(2022) Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose
Dryad Digital Repository, doi:10.5061/dryad.rfj6q57ds.

https://dx.doi.org/10.5061/dryad.rfj6q57ds

Article and author information

Author details

Isabella Tomanek

Institute of Science and Technology Austria, Klosterneuburg, Austria

Competing interests
The authors declare that no competing interests exist.
Calin Guet

Institute of Science and Technology Austria, Klosterneuburg, Austria

For correspondence
calin@ist.ac.at

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6220-2052

Funding

No external funding was received for this work.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.