Studying Evolutionary Change: Transdisciplinary Advances in Understanding and Measuring Evolution

Evolutionary processes can be found in almost any historical, i.e. evolving, system that erroneously copies from the past. Well studied examples do not only originate in evolutionary biology but also in historical linguistics. Yet an approach that would bind together studies of such evolving systems is still elusive. This thesis is an attempt to narrowing down this gap to some extend. An evolving system can be described using characters that identify their changing features. While the problem of a proper choice of characters is beyond the scope of this thesis and remains in the hands of experts we concern ourselves with some theoretical as well data driven approaches. Having a well chosen set of characters describing a system of different entities such as homologous genes, i.e. genes of same origin in different species, we can build a phylogenetic tree. Consider the special case of gene clusters containing paralogous genes, i.e. genes of same origin within a species usually located closely, such as the well known HOX cluster. These are formed by step- wise duplication of its members, often involving unequal crossing over forming hybrid genes. Gene conversion and possibly other mechanisms of concerted evolution further obfuscate phylogenetic relationships. Hence, it is very difficult or even impossible to disentangle the detailed history of gene duplications in gene clusters. Expanding gene clusters that use unequal crossing over as proposed by Walter Gehring leads to distinctive patterns of genetic distances. We show that this special class of distances helps in extracting phylogenetic information from the data still. Disregarding genome rearrangements, we find that the shortest Hamiltonian path then coincides with the ordering of paralogous genes in a cluster. This observation can be used to detect ancient genomic rearrangements of gene clus- ters and to distinguish gene clusters whose evolution was dominated by unequal crossing over within genes from those that expanded through other mechanisms. While the evolution of DNA or protein sequences is well studied and can be formally described, we find that this does not hold for other systems such as language evolution. This is due to a lack of detectable mechanisms that drive the evolutionary processes in other fields. Hence, it is hard to quantify distances between entities, e.g. languages, and therefore the characters describing them. Starting out with distortions of distances, we first see that poor choices of the distance measure can lead to incorrect phylogenies. Given that phylogenetic inference requires additive metrics we can infer the correct phylogeny from a distance matrix D if there is a monotonic, subadditive function ζ such that ζ^−1(D) is additive. We compute the metric-preserving transformation ζ as the solution of an optimization problem. This result shows that the problem of phylogeny reconstruction is well defined even if a detailed mechanistic model of the evolutionary process is missing. Yet, this does not hinder studies of language evolution using automated tools. As the amount of available and large digital corpora increased so did the possibilities to study them automatically. The obvious parallels between historical linguistics and phylogenetics lead to many studies adapting bioinformatics tools to fit linguistics means. Here, we use jAlign to calculate bigram alignments, i.e. an alignment algorithm that operates with regard to adjacency of letters. Its performance is tested in different cognate recognition tasks. Using pairwise alignments one major obstacle is the systematic errors they make such as underestimation of gaps and their misplacement. Applying multiple sequence alignments instead of a pairwise algorithm implicitly includes more evolutionary information and thus can overcome the problem of correct gap placement. They can be seen as a generalization of the string-to-string edit problem to more than two strings. With the steady increase in computational power, exact, dynamic programming solutions have become feasible in practice also for 3- and 4-way alignments. For the pairwise (2-way) case, there is a clear distinction between local and global alignments. As more sequences are consid- ered, this distinction, which can in fact be made independently for both ends of each sequence, gives rise to a rich set of partially local alignment problems. So far these have remained largely unexplored. Thus, a general formal frame- work that gives raise to a classification of partially local alignment problems is introduced. It leads to a generic scheme that guides the principled design of exact dynamic programming solutions for particular partially local alignment problems

cii Student Papers - 2021

In this collection of papers, we, the Research Group Critical Information Infrastructures (cii) from the Karlsruhe Institute of Technology, present nine selected student research articles contributing to the design, development, and evaluation of critical information infrastructures. During our courses, students mostly work in groups and deal with problems and issues related to sociotechnical challenges in the realm of (critical) information systems. Student papers came from four different cii courses, namely Emerging Trends in Digital Health, Emerging Trends in Internet Technologies, Critical Information Infrastructures, and Digital Health in the winter term of 2020 and summer term of 2021

Dynamics of DNA methylation in differentiating hematopoietic cells

The methylation of CpG dinucleotides represents an epigenetic mark that is crucial for regulating the normal progression of numerous biological processes including development and cell differentiation. During the last decade, it became increasingly clear that methylation patterns are not static but may adapt to various cellular requirements. Regarding normal somatic cells, the dynamic of DNA methylation including its extent throughout the genome as well as its implication in cellular differentiation is largely unknown. In the context of the present thesis, it was demonstrated that several cell type or cell lineage specific genes harboured a specific methylation profile. Interestingly, those differences in DNA methylation were mostly confined to regions upstream or downstream of the core promoter and preferentially affected CpG poor DNA regions. The gene regulatory relevance of DNA sequences affected by dynamical alterations in the methylation pattern, may be studied by means of transient transfection assays. For this purpose, a novel CpG free luciferase reporter vector was designed that provides a simple and robust tool for analysing effects of DNA methylation within CpG poor as well as CpG rich DNA stretches on gene expression. As particularly the regulated and active removal of methyl CpG marks still remains controversial, the major aim of the present work was the characterization of this epigenetic phenomenon in a natural setting of post mitotic cells: the proliferation independent differentiation of human peripheral blood monocytes into dendritic cells or macrophages, respectively. Using a global, comparative CpG methylation profiling approach that was directed to detect differentially methylated regions in CpG rich as well as CpG poor DNA stretches, 45 examples for active demethylation were identified. The validation by a bisulfite conversion based technique and the characterization of a selected subset revealed that DNA demethylation was not restricted to promoter regions and that the time course varied for individual CpGs. Irrespective of their location, the removal of methylated cytosines strictly coincided with the appearance of activating histone marks indicating the presence of cis acting elements. Since demethylation events were highly reproducible between monocyte derived dendritic cells from distinct donors, the present data suggest that active demethylation is a precisely targeted process. The comparison of the global methylation data with the genome wide mRNA expression profiles demonstrated that active DNA demethylation is not always directly followed by transcriptional activation. Probably, gene activation is a multilevel process that is dependent on various genetic and epigenetic factors. Thereby, CpG demethylation seems to be a necessary prerequisite for priming the chromatin structure for transcription factor binding

Efficient Change Management of XML Documents

XML-based documents play a major role in modern information architectures and their corresponding work-flows. In this context, the ability to identify and represent differences between two versions of a document is essential. A second important aspect is the merging of document versions, which becomes crucial in parallel editing processes. Many different approaches exist that meet these challenges. Most rely on operational transformation or document annotation. In both approaches, the operations leading to changes are tracked, which requires corresponding editing applications. In the context of software development, however, a state-based approach is common. Here, document versions are compared and merged using external tools, called diff and patch. This allows users for freely editing documents without being tightened to special tools. Approaches exist that are able to compare XML documents. A corresponding merge capability is still not available. In this thesis, I present a comprehensive framework that allows for comparing and merging of XML documents using a state-based approach. Its design is based on an analysis of XML documents and their modification patterns. The heart of the framework is a context-oriented delta model. I present a diff algorithm that appears to be highly efficient in terms of speed and delta quality. The patch algorithm is able to merge document versions efficiently and reliably. The efficiency and the reliability of my approach are verified using a competitive test scenario