| Entwicklung und Anwendung neutraler Modelle zur Beschreibung der Evolution von Genexpression | |
Abstract/OtherAbstract
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Recent studies describe that the level of gene expression between species is positively correlated with the time that has passed since the species split from a common ancestor (Ranz and Machado, 2006). Moreover, Khaitovich et al. (2004) found a linear relationship between divergence time and expression differences. This linearity can be explained by the neutral theory (Kimura, 1983). Consequently, a neutral model for gene expression evolution was suggested (Khaitovich et al., 2005). The model describes mutations in the regulatory region of a gene by a compound Poisson process. The strength of changes in the expression level is described by a continuous distribution, the so-called mutation effect distribution. That is, whenever a mutation occurs, the gene expression level changes according to the mutation effect distribution. In this thesis the model by Khaitovich et al. (2005) is extended in two ways. In a first extension a gamma distribution is used to describe mutation effects which is more flexible than the distributions used in the original model. In a second extension, non-mutational effects are taken into account. These effects (e.g., metabolism and environmental effects) overlay mutational changes of gene expression. To describe them a new parameter is introduced which provides a better fit to evolutionary data. This makes it possible to estimate influences of mutational and non-mutational changes on the gene expression level. According to this, a Bayesian method to detect genes with mutations in their regulatory regions is suggested. Furthermore, a non-neutrality test is presented which can be applied to gene expression data sampled from individuals of a population. Based on this test one can detect those genes that show a significant deviation from expression levels under neutrality. The test is an adaptation of the widely used Tajima’s D test (Tajima, 1989). Finally, a medical application is applied in which carcinogenesis is considered as an evolutionary process. All described models and methods in this thesis are evaluated with synthetic data and applied to biological data. |
Authors
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Rosskopf, Michael |
Contributors
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Haeseler, Arndt von, Michael Leuschel |
Publication Detail
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Publisher : - Type : Dissertation Format : Text |
Date Detail
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2007-06-25 |
Subject
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004, neutral theory evolution gene expression stochastic models |
Coverage
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Relation
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Source
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Khaitovich, P., Pääbo, S. and Weiss, G. (2005) Towards a neutral evolutionary model of gene expression. Genetics, 170, 929–939. Khaitovich, P., Weiss, G., Lachmann, M., Hellmann, I., Enard, W., Muetzel, B., Wirkner, U., Ansorge, W. and Pääbo, S. (2004) A neutral model of transcriptome evolution. PLoS Biology, 2, 682–689. Kimura, M. (1983) The neutral theory. Cambridge University Press, Cambridge, UK. Ranz, J.-M. and Machado, C.-A. (2006) Uncovering evlutionary patterns of gene expression using microarrays. Trends in Ecology and Evolution, 21, 29–37. Tajima, F. (1989) Statistical method for testing the neutral mutation hypothesis by dna polymorphism. Genetics, 123, 585–595. |
Copyright Information
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free |
Other Details
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Languages : ger |
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