TY - JOUR AB - 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. AU - Tomanek, Isabella AU - Guet, Calin C ID - 12333 JF - eLife TI - Adaptation dynamics between copynumber and point mutations VL - 11 ER - TY - GEN AB - 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. AU - Tomanek, Isabella AU - Guet, Calin C ID - 12339 TI - Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose ER - TY - GEN AB - The main idea behind the Core Project is to teach first year students at IST scientific communication skills and let them practice by presenting their research within an interdisciplinary environment. Over the course of the first semester, students participated in seminars, where they shared their results with the colleagues from other fields and took part in discussions on relevant subjects. The main focus during this sessions was on delivering the information in a simplified and comprehensible way, going into the very basics of a subject if necessary. At the end, the students were asked to present their research in the written form to exercise their writing skills. The reports were gathered in this document. All of them were reviewed by the teaching assistants and write-ups illustrating unique stylistic features and, in general, an outstanding level of writing skills, were honorably mentioned in the section "Selected Reports". AU - Maslov, Mikhail AU - Kondrashov, Fyodor AU - Artner, Christina AU - Hennessey-Wesen, Mike AU - Kavcic, Bor AU - Machnik, Nick N AU - Satapathy, Roshan K AU - Tomanek, Isabella ID - 8151 TI - Core Project Proceedings ER - TY - JOUR AB - 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. AU - Tomanek, Isabella AU - Grah, Rok AU - Lagator, M. AU - Andersson, A. M. C. AU - Bollback, Jonathan P AU - Tkačik, Gašper AU - Guet, Calin C ID - 7652 IS - 4 JF - Nature Ecology & Evolution SN - 2397-334X TI - Gene amplification as a form of population-level gene expression regulation VL - 4 ER - TY - THES AB - Mutations are the raw material of evolution and come in many different flavors. Point mutations change a single letter in the DNA sequence, while copy number mutations like duplications or deletions add or remove many letters of the DNA sequence simultaneously. Each type of mutation exhibits specific properties like its rate of formation and reversal. Gene expression is a fundamental phenotype that can be altered by both, point and copy number mutations. The following thesis is concerned with the dynamics of gene expression evolution and how it is affected by the properties exhibited by point and copy number mutations. Specifically, we are considering i) copy number mutations during adaptation to fluctuating environments and ii) the interaction of copy number and point mutations during adaptation to constant environments.   AU - Tomanek, Isabella ID - 8653 KW - duplication KW - amplification KW - promoter KW - CNV KW - AMGET KW - experimental evolution KW - Escherichia coli SN - 2663-337X TI - The evolution of gene expression by copy number and point mutations ER - TY - DATA AB - Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where 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 expression of any gene, without leaving any genomic signature. AU - Tomanek, Isabella ID - 7016 KW - Escherichia coli KW - gene amplification KW - galactose KW - DOG KW - experimental evolution KW - Illumina sequence data KW - FACS data KW - microfluidics data TI - Data for the paper "Gene amplification as a form of population-level gene expression regulation" ER -