thesis Isabella Tomanek author 3981F020-F248-11E8-B48F-1D18A9856A870000-0001-6197-363X Calin C Guet author 47F8433E-F248-11E8-B48F-1D18A9856A870000-0001-6220-2052 CaGu department 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 sequence 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 system that allows us to distinguish 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 selected for: In conditions of high gene expression demand, the two types of mutations occur as a combination. Under low gene expression demand, negative epistasis between the two types of mutations renders them mutually exclusive. Thus, owing to their higher frequency, adaptation is dominated by copy-number mutations. Ultimately, due to high rates of reversal 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. Dryad2022 10.5061/dryad.rfj6q57ds https://research-explorer.ista.ac.at/record/12333 Tomanek, Isabella, and Calin C. Guet. <i>Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose</i>. Dryad, 2022, doi:<a href="https://doi.org/10.5061/dryad.rfj6q57ds">10.5061/dryad.rfj6q57ds</a>. I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose.” Dryad, 2022. Tomanek I, Guet CC. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. 2022. doi:<a href="https://doi.org/10.5061/dryad.rfj6q57ds">10.5061/dryad.rfj6q57ds</a> I. Tomanek, C.C. Guet, (2022). Tomanek, I., &#38; Guet, C. C. (2022). Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. Dryad. <a href="https://doi.org/10.5061/dryad.rfj6q57ds">https://doi.org/10.5061/dryad.rfj6q57ds</a> Tomanek, Isabella, and Calin C Guet. “Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose.” Dryad, 2022. <a href="https://doi.org/10.5061/dryad.rfj6q57ds">https://doi.org/10.5061/dryad.rfj6q57ds</a>. Tomanek I, Guet CC. 2022. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose, Dryad, <a href="https://doi.org/10.5061/dryad.rfj6q57ds">10.5061/dryad.rfj6q57ds</a>. 123392023-01-23T09:00:37Z2025-03-06T14:03:50Z