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  Models for processes of somatic evolution on multiple scales

Böttcher, M. A. (2018). Models for processes of somatic evolution on multiple scales. PhD Thesis, University of Lübeck, Lübeck.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-9C30-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-9C31-7
Genre: Thesis


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Böttcher, Marvin A.1, Author              
Traulsen, Arne1, Referee              
Busch, Hauke, Referee
1Department Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445641              


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 Abstract: One of the main conditions for multicellularity is the limitation of long-term evolutionary success of the somatic cells within an organism. The somatic cells often constitute the vast majority of a multicellular organism. However, by definition they have no chance to give their genome to the next generation of the organism and merely act as a container for the successful reproduction of the few germ line cells. Since nutrients and space are limited within a multicellular organism, a careful coordination of the somatic cells in the tissue, along with a limitation of proliferation and strict control over cell function, is paramount for the evolutionary success of the organism. However, due to somatic mutations this balance can be disturbed such that somatic cells regain proliferative ability and outcompete other cells within the organism. This somatic evolution can ultimately lead to cancer or cancer-like phenomena with unlimited growth of specific clones, which can be lethal for the multicellular organism. In this work I will present four different mathematical models showcasing processes of somatic evolution. Both main ingredients of evolution — variation and selection — will be shown in different examples in systems of different scales. Firstly, on the molecular level, the basis for evolutionary processes of cells is the long term storage of genetic information and the process of how this information is converted into functional proteins. Slight changes in this process can have major consequences for the affected cells, also and especially for somatic cells embedded into multicellular organisms. Here, I will present a model for the translation of RNA into functional protein which takes circularization of RNA into account. This reveals a potential mechanisms for a fitness effect of synonymous mutations, that is mutations that do not alter the protein produced. Secondly, on a larger scale, the strict coordination of often billions of somatic cells requires sophisticated tissue structures. These tissue structures can have a strong impact on the somatic evolution of cells within the tissue. Since mutations mainly arise on cell divisions, replicative age of cells in these structures is tightly controlled and mutation accumulation is highly irregular across different cell types. I will show how a measurable replicative age distribution might provide insight into specific tissue dynamics of a hierarchically structured tissue such as blood. Thirdly, tissue structure also has a strong impact on selection of previously emerged mutants, as mutations can have varying fitness effects in different cell types. In this i work I will examine this for the example of chronic myeloid leukemia, a malignancy which is caused by a known somatic mutation for which nowadays specific targeted treatment is available. Finally, evolution, and specifically evolution of somatic cells, has to be seen within the environment and the ecological niche of the evolving cells, since successful traits always depend on the momentary environment. In the context of cancer this environment is often set by the treatment of the disease which shapes the growth and extinction of cancer cells, which I will explore in more detail in this work. Overall, the models presented in this work demonstrate mechanisms for observable patterns in biological systems in the context of somatic evolution. This also shows how experimental observations or data from clinical studies can be combined with insights from theoretical models for a deeper understanding of somatic evolution on the molecular scale, intercellular scale, or to support the treatment of cancer.


Language(s): eng - English
 Dates: 2018-09-112018-09-11
 Publication Status: Published in print
 Pages: 141
 Publishing info: Lübeck : University of Lübeck
 Table of Contents: -
 Rev. Method: -
 Identifiers: Other: Diss/13027
 Degree: PhD



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