Universiẗat, Diss.--Hannover, 1994.

Universiẗat, Diss.--Kaiserslautern, 1999.

Univ., Diss.--Regensburg, 1999.

The evolution of biological species depends on changes in genes. Among these changes are the gradual accumulation of DNA mutations, insertions and deletions, duplication of genes, movements of genes within and between chromosomes, gene losses and gene transfer. As two populations of the same species evolve independently, they will eventually become reproductively isolated and become two distinct species. The evolutionary history of a set of related species through the repeated occurrence of this speciation process can be represented as a tree-like structure, called a phylogenetic tree or a species tree. Since duplicated genes in a single species also independently accumulate point mutations, insertions and deletions, they drift apart in composition in the same way as genes in two related species. The divergence of all the genes descended from a single gene in an ancestral species can also be represented as a tree, a gene tree that takes into account both speciation and duplication events. In order to reconstruct the evolutionary history from the study of extant species, we use sets of similar genes, with relatively high degree of DNA similarity and usually with some functional resemblance, that appear to have been derived from a common ancestor. The degree of similarity among different instances of the “same gene” in different species can be used to explore their evolutionary history via the reconstruction of gene family histories, namely gene trees. Orthology refers specifically to the relationship between two genes that arose by a speciation event, recent or remote, rather than duplication. Comparing orthologous genes is essential to the correct reconstruction of species trees, so that detecting and identifying orthologous genes is an important problem, and a longstanding challenge, in comparative and evolutionary genomics as well as phylogenetics. A variety of orthology detection methods have been devised in recent years. Although many of these methods are dependent on generating gene and/or species trees, it has been shown that orthology can be estimated at acceptable levels of accuracy without having to infer gene trees and/or reconciling gene trees with species trees. Therefore, there is good reason to look at the connection of trees and orthology from a different angle: How much information about the gene tree, the species tree, and their reconciliation is already contained in the orthology relation among genes? Intriguingly, a solution to the first part of this question has already been given by Boecker and Dress [Boecker and Dress, 1998] in a different context. In particular, they completely characterized certain maps which they called symbolic ultrametrics. Semple and Steel [Semple and Steel, 2003] then presented an algorithm that can be used to reconstruct a phylogenetic tree from any given symbolic ultrametric. In this thesis we investigate a new characterization of orthology relations, based on symbolic ultramterics for recovering the gene tree. According to Fitch’s definition [Fitch, 2000], two genes are (co-)orthologous if their last common ancestor in the gene tree represents a speciation event. On the other hand, when their last common ancestor is a duplication event, the genes are paralogs. The orthology relation on a set of genes is therefore determined by the gene tree and an “event labeling” that identifies each interior vertex of that tree as either a duplication or a speciation event. In the context of analyzing orthology data, the problem of reconciling event-labeled gene trees with a species tree appears as a variant of the reconciliation problem where genes trees have no labels in their internal vertices. When reconciling a gene tree with a species tree, it can be assumed that the species tree is correct or, in the case of a unknown species tree, it can be inferred. Therefore it is crucial to know for a given gene tree whether there even exists a species tree. In this thesis we characterize event-labelled gene trees for which a species tree exists and species trees to which event-labelled gene trees can be mapped. Reconciliation methods are not always the best options for detecting orthology. A fundamental problem is that, aside from multicellular eukaryotes, evolution does not seem to have conformed to the descent-with-modification model that gives rise to tree-like phylogenies. Examples include many cases of prokaryotes and viruses whose evolution involved horizontal gene transfer. To treat the problem of distinguishing orthology and paralogy within a more general framework, graph-based methods have been proposed to detect and differentiate among evolutionary relationships of genes in those organisms. In this work we introduce a measure of orthology that can be used to test graph-based methods and reconciliation methods that detect orthology. Using these results a new algorithm BOTTOM-UP to determine whether a map from the set of vertices of a tree to a set of events is a symbolic ultrametric or not is devised. Additioanlly, a simulation environment designed to generate large gene families with complex duplication histories on which reconstruction algorithms can be tested and software tools can be benchmarked is presented.

In der vorliegenden Studie haben wir mit Hilfe von SHARP-Screening, einer 16S-rRNA-basierten Heterogenitäts- und phylogenetischen Analyse, die mikrobielle Diversität in entzündlichen Lymphadenitiden ohne vorherige Kenntnis der jeweiligen Erreger an einer Serie von 15 Lymphknoten untersucht. Die Methode wurde erstmals auf diese Fragestellung angewandt. Sie konnte für die Verwendung von paraffineingebettetem Gewebe adaptiert werden, so dass auch Gewebeproben analysiert werden konnten, von denen kein Gefriermaterial zur Verfügung stand und die in Routineverfahren eingebettet und nach Standardmethoden gefärbt wurden. SHARP-Screening beinhaltet zwei komplementäre Schritte: Zuerst erfolgte die Erstellung einer Genbank aller bakteriellen Gene aus der gesamten extrahierten DNA des analysierten Gewebes durch gezielte Amplifikation des 16S-rRNA-Gens mittels universeller eubakterieller Primer. Als zweiter Schritt wurde nach der Transformation mittels Analyse des Restriktionsfragmentlängenpolymorphismus die Selektion der jeweiligen unterschiedlichen Phylotypen der enthaltenen 16S-rRNA-Gene durchgeführt (insgesamt 400). Nach der Sequenzierung wurden die 16S-rRNA-Gene durch den Vergleich mit bekannten bakteriellen Sequenzen mit Hilfe des „Basic-Local-Alignment-Search-Tool“ (BLAST) identifiziert. SHARP-Screening hat sich als geeignete Methode zur Analyse der gesamten, in einer Gewebeprobe enthaltenen bakteriellen Flora erwiesen. Dabei wurden zum Teil andere Erreger gefunden, als aus dem histologischen Bild vermutet wurden. So konnte zum Beispiel mit dem Nachweis von Gluconacetobacter sacchari, als potentieller Erreger einer septischen Granulomatose, eine alternative Differentialdiagnose zur histologisch vermuteten Katzenkratzkrankheit aufgezeigt werden. Darüber hinaus konnten auch gleichartige histologische Bilder bei dem gleichen identifizierten Erreger beobachtet werden. Zum Beispiel konnten im Zusammenhang mit dem Auftreten von Ödemen, Nekrosen, granulomatös eitrigen Veränderungen und einer ausgeprägten Sinus-histiozytose im Lymphknotengewebe immer wieder Comamonadaceae bzw. Janthinobacterium nachgewiesen werden. Oft zeigte sich nicht ein einzelner Erreger der Lymphadenitis, sondern ein ganzes Spektrum, wobei aus dem Vorhandensein der 16S-rRNA nicht auf das Vorhandensein vitaler Erreger geschlossen werden kann. Dennoch erlaubt die Häufigkeit der entsprechenden Klone eine semiquantitative Abschätzung der Bedeutung des jeweiligen Erregers. So wies SHARP-Screening auch Homologien zu Paracoccus yeeii nach. Eine Spezies, die mit klassischen Methoden häufig übersehen wird, die in Lymphknoten jedoch eine pathogene Rolle spielen kann. Im Zusammenhang mit dem histologischen Verdacht auf ein Malignom wurden in einigen Fällen Streptomyces, Roseomonas gilardii rosea und Stenotrophomonas maltophila nachgewiesen, die auch in der Literatur häufig bei immunsupprimierten Patienten vorkommen. Bei dem Verdacht auf ein Lymphgranuloma venerum wurde eine Cyanobacterium-Spezies detektiert, die es nach Literaturangaben Chlamydia trachomatis erst möglich macht, den eigenen Aminosäurestoffwechsel zu betreiben. Insgesamt dürften vom SHARP-Screening noch weitere tiefgreifende Erkenntnisse der bakteriellen Diversität und kausaler Erregerassoziationen in Erkrankungen des lymphatischen Systems zu erwarten sein. / The focus of this study was laid on the analysis of the microbial diversity in inflammatory lymphadenitis of 15 different lymph nodes without prior knowledge of the respective causative organism with help of the SHARP-Screening, a 16S-rRNA-based heterogeneity and phylogenetic analysis. This represents the first study to analyse this problem with the above mentioned SHARP-Screening adapting the method for the utilization of paraffin embedded tissue which consequently allowed the analysis of tissue specimen of which no freezing material was available and which were embedded in routine procedures as well as coloured according to a standard approach. The SHARP-Screening compromises two complementary steps: The first step is the creation of a gene pool of all bacterial genes of the entire DNA extracted from the analysed tissue by the systematic amplification of the 16S-rRNA-gene by means of universal eubacterial primers. The next step after the transformation was the selection of the different phylotypes of the incorporated 16S-rRNA-genes (altogether 400) by analysing the restriction fragment length polymorphism (RFLP). After the sequencing, the 16S-rRNA-genes were identified by comparing them with the known bacterial sequences with help of the “Basic-Local-Alignment-Search-Tool” (BLAST). The SHARP-Screening has proved itself as an adequate method to analyse the entire bacterial flora contained in the tissue sample. In some cases different causative organisms were found in contrast to the expectations which arose from the histological pictures. In this way evidence of gluconacetobacter sacchari could be provided as potential causative agents of a septic granulomatosis, an alternative differential diagnosis to the histologically assumed cat scratch disease. Furthermore, histological pictures of a similar type could be observed with regard to the same identified causative organism. For example, in conjunction with the appearance of edema, necrosis, granulomatosic purulent alterations and a very pronounced sinushistiozytosis in the lymph node tissue, comamonadaceae and accordingly janthinobacteria could consistently be demonstrated. A lot of times not just a single causative organism but a whole spectrum of the lymphadenitis could be identified. Here, however, the existence of the 16S-rRNA cannot be attributed to the existence of vital causative agents. Nevertheless, the frequency of the respective clones allows a semi quantitative assessment of the importance of the corresponding causative agents. Thus the SHARP-Screening proved evidence of homologies to paracoccus yeeii. A species which is often missed with classic methods however can play a pathogenic role. In several cases streptomyces, roseomonas gilardii rosea and stenotrophomonas maltophila, which are often mentioned in literature with regard to immunosuppressed patients, could be demonstrated in connection with the histological suspicion of a malignant tumour. While suspecting a lymphgranuloma venerum, a cyanobacterium species was discovered which according to literature sources enables chlamydia trachomatis to operate the body’s amino acid metabolism. Altogether, the SHARP-Screening is expected to lead to even more profound findings of bacterial diversity and causal causative organism associations with regard to diseases of the lymphatic system.

The evolution of biological species depends on changes in genes. Among these changes are the gradual accumulation of DNA mutations, insertions and deletions, duplication of genes, movements of genes within and between chromosomes, gene losses and gene transfer. As two populations of the same species evolve independently, they will eventually become reproductively isolated and become two distinct species. The evolutionary history of a set of related species through the repeated occurrence of this speciation process can be represented as a tree-like structure, called a phylogenetic tree or a species tree. Since duplicated genes in a single species also independently accumulate point mutations, insertions and deletions, they drift apart in composition in the same way as genes in two related species. The divergence of all the genes descended from a single gene in an ancestral species can also be represented as a tree, a gene tree that takes into account both speciation and duplication events. In order to reconstruct the evolutionary history from the study of extant species, we use sets of similar genes, with relatively high degree of DNA similarity and usually with some functional resemblance, that appear to have been derived from a common ancestor. The degree of similarity among different instances of the “same gene” in different species can be used to explore their evolutionary history via the reconstruction of gene family histories, namely gene trees. Orthology refers specifically to the relationship between two genes that arose by a speciation event, recent or remote, rather than duplication. Comparing orthologous genes is essential to the correct reconstruction of species trees, so that detecting and identifying orthologous genes is an important problem, and a longstanding challenge, in comparative and evolutionary genomics as well as phylogenetics. A variety of orthology detection methods have been devised in recent years. Although many of these methods are dependent on generating gene and/or species trees, it has been shown that orthology can be estimated at acceptable levels of accuracy without having to infer gene trees and/or reconciling gene trees with species trees. Therefore, there is good reason to look at the connection of trees and orthology from a different angle: How much information about the gene tree, the species tree, and their reconciliation is already contained in the orthology relation among genes? Intriguingly, a solution to the first part of this question has already been given by Boecker and Dress [Boecker and Dress, 1998] in a different context. In particular, they completely characterized certain maps which they called symbolic ultrametrics. Semple and Steel [Semple and Steel, 2003] then presented an algorithm that can be used to reconstruct a phylogenetic tree from any given symbolic ultrametric. In this thesis we investigate a new characterization of orthology relations, based on symbolic ultramterics for recovering the gene tree. According to Fitch’s definition [Fitch, 2000], two genes are (co-)orthologous if their last common ancestor in the gene tree represents a speciation event. On the other hand, when their last common ancestor is a duplication event, the genes are paralogs. The orthology relation on a set of genes is therefore determined by the gene tree and an “event labeling” that identifies each interior vertex of that tree as either a duplication or a speciation event. In the context of analyzing orthology data, the problem of reconciling event-labeled gene trees with a species tree appears as a variant of the reconciliation problem where genes trees have no labels in their internal vertices. When reconciling a gene tree with a species tree, it can be assumed that the species tree is correct or, in the case of a unknown species tree, it can be inferred. Therefore it is crucial to know for a given gene tree whether there even exists a species tree. In this thesis we characterize event-labelled gene trees for which a species tree exists and species trees to which event-labelled gene trees can be mapped. Reconciliation methods are not always the best options for detecting orthology. A fundamental problem is that, aside from multicellular eukaryotes, evolution does not seem to have conformed to the descent-with-modification model that gives rise to tree-like phylogenies. Examples include many cases of prokaryotes and viruses whose evolution involved horizontal gene transfer. To treat the problem of distinguishing orthology and paralogy within a more general framework, graph-based methods have been proposed to detect and differentiate among evolutionary relationships of genes in those organisms. In this work we introduce a measure of orthology that can be used to test graph-based methods and reconciliation methods that detect orthology. Using these results a new algorithm BOTTOM-UP to determine whether a map from the set of vertices of a tree to a set of events is a symbolic ultrametric or not is devised. Additioanlly, a simulation environment designed to generate large gene families with complex duplication histories on which reconstruction algorithms can be tested and software tools can be benchmarked is presented.

Parareptilien stellen ein artenreiches Monophylum paläozoischer und früh-mesozoischer Amnioten dar; sie bilden innerhalb der Reptilien die Schwestergruppe zu den Eureptilien. Pareiasaurier, eine Untergruppe der Parareptilien, sind eine bedeutende Komponente spät-permischer …kosysteme. Jüngst wurde ein Schwestergruppenverhältnis zu den Nycyeroletern entdeckt, mit welchen sie die "Pareiasauromorpha" bilden. Diese Arbeit befasst sich mit der Beschreibung einiger dieser bisher schlecht untersuchten Parareptilien und deren Verwandtschaftsverhältnisse.Der Pareiasaurier Deltavjatia vjatkensis und der Nycteroleter Emeroleter levis aus der russischen Lokalität Kotel''nich werden mithilfe neu entdeckten Materials im Detail beschrieben. Das gut erhaltene Deltavjatja Materials umfasst mehrere Grössenstadien und erlaubt eine Analyse der Wachstumsraten. Eine geometrisch-morphometrische Analyse des Schädeldachs lässt eine allometrische Zunahme von Schnauzenlänge und Postorbitalregion erkennen. Auch wird der historisch erste Pareiasaurier, Parasaurus geinitzi, aus dem oberpermischen Kupferschiefer von Deutschland neu beschrieben. Zudem ergibt eine Neuanalyse der russischen Nycteroleter eine Synonymie von Tokosaurus perforatus und Macroleter poezicus. Eine phylogenetische Analyse unter Verwendung von Parsimonie und bayesischen Methoden ergibt eine basale Stellung von Parasaurus und eine Monophylie der Nycteroleter; letztere wird aber nur durch die Parsimonie unterstützt. Alle phylogenetischen Methoden ergeben jedoch eine Monophylie der Pareiasauromorpha. Eine strato-kladistische Analyse zeigt zudem eine ähnliche Topologie. Eine biogeographische Analyse der Pareiasauromorpha ergibt mehrfache Verbreitungsereignisse nach Russland und China. Diese stimmen überein mit denen anderer oberpermischer Gruppen, jedoch werden nur wenige dieser Ereignisse komplett bei allen Taxa gefunden. / Parareptilia is a diverse, yet enigmatic clade of fossil amniotes, sister-group to Eureptilia within Reptilia. Pareiasauria, a widely distributed and speciose parareptile group, was a prominent part of Late Permian ecosystems, yet few taxa have been examined in detail. This work describes some poorly known parareptiles, using this data to assess interrelationships and evaluate evolutionary trends within the clade. A reassessment of a group of derived parareptiles, the Russian ''nycteroleters'', results in the synonymy of Tokosaurus perforatus with Macroleter poezicus. A phylogenetic analysis of parareptilian relationships recovers a ''nycteroleter'' monophyly in the parsimony analysis, but not with Bayesian, with the genus Bashkyroleter paraphyletic in both. A monophyletic clade consisting of the nycteroleters and pareiasaurs, termed Pareiasauromorpha, is supported by all methods. Parasaurus geinitzi von Mayer, 1857 is redescribed and confirmed to be a pareiasaur based on the anatomy of the type specimens and fragmentary material that has subsequently been assigned to the taxon. Well-preserved cranial and postcranial material of the pareiasaur Deltavjatia vjatkensis from Kotel''nich, Russia, is described in detail for the first time, including specimens of radically different size classes. The first geometric morphometric analysis of a parareptile reveals an allometric increase in snout length along with an increase in postorbital length. A reassessment of the relationships of Pareiasauromorpha using different methods of phylogenetic inference recovers similar results. The topologies are not well supported, but are relatively consistent with the stratigraphic record. Biogeographic analysis of pareiasauromorph taxa recovers complex and reticulated patterns of dispersal and vicariance, including multiple dispersal events into both Russia and China; patterns that are consistent with those seen in other Late Permian groups, though few events are shared by all clades.

The presented study comprises a complete morphological and phylotaxonomic revision of basal Sphenacodontia, designated as the paraphyletic ‘haptodontines’. Ianthodon from the Kasimovian is known from newly identified elements, including most of the skull and particular postcrania. This species is determined as the best model for the initial morphology of the Sphenacomorpha (Edaphosauridae and Sphenacodontia). Remarkably older sphenacodontian remains from the Moscovian indicate a derived, though fragmentarily known form, possibly basal Sphenacodontoidea. The genus Haptodus is conclusively revised, including the revalidation of the type species H. baylei from the Artinskian. Haptodus grandis is renamed as Hypselohaptodus, gen. nov. “Haptodus” garnettensis is not monophyletic with Haptodus, moreover the material assigned to it yielded a greater diversity. Thus, its renaming includes Eohaptodus garnettensis, gen. nov., Tenuacaptor reiszi, gen. et spec. nov., and Kenomagnathus scotti, gen. et spec. nov. Along with Ianthodon and the basal edaphosaurid Ianthasaurus, these taxa from a single assemblage are differentiated by dentition and skull proportions, providing a case study of annidation. Since Ianthodon can be excluded from Sphenacomorpha, the larger, stem-based taxon Haptodontiformes is introduced. More derived ‘haptodontines’ apparently form another radiation, named as Pantherapsida. This new taxon includes Cutleria, Tetraceratops, Hypselohaptodus, the Palaeohatteriidae (Pantelosaurus and Palaeohatteria), and the Sphenacodontoidea. The ‘pelycosaur’-therapsid transition is affirmed as a long-term development. An integrative evolutionary hypothesis of basal sphenacodontians is provided, within which the ghost lineage of Early Permian therapsids can be explained by biome shift.

In diese Dissertation, Ich konzentriere mich insbesondere darauf, wie die Artbestimmung in der Gattung Eimeria mit der Wirtsspezifität bei Nagetierarten zusammenhängt. Zunächst bietet diese Arbeit eine Reihe von Methoden zur Beurteilung der Prävalenz auf der Ebene der Parasitenarten in Mus musculus. Als Ergebnis war es möglich, drei verschiedene Eimeria-Spezies zu identifizieren, Mäuse mit Doppelinfektionen zu erkennen und die artenspezifische Prävalenz in Abhängigkeit von der Wirtsdichte vorherzusagen. Zur Identifizierung von Eimeria spp. über verschiedene Wirtsarten hinweg wurde eine neuartige Hochdurchsatz-Multi-Locus-Genotypisierungsmethode etabliert und mit der auf zuvor etablierten Markern basierenden Einzelmarker-Genotypisierung verglichen. Dies bestätigte, dass die Art E. falciformis in einer einzigen Wirtsart, der Hausmaus, vorkommt. E. vermiformis und E. apionodes konnten jedoch nicht unterschieden werden, was auf eine einzige Art mit breitem Wirtsspektrum hindeutet. E. vermiformis und E. apionodes konnten jedoch nicht unterschieden werden, was auf eine einzige Art mit breiter Wirtsverwendung in einem phylogenetischen Artkonzept schließen lässt. Diese Ergebnisse zeigen, dass die hohe Wirtsspezifität, die traditionell für Eimeria-Parasiten angenommen wird, fragwürdig ist und dass die Identifizierung von Arten durch Wirtsassoziation vermieden werden sollte. Durch molekulare Amplifikation, Sequenzierung, Genotypisierung und phylogenetische Analyse war es möglich, Eimerien auf Artniveau zu identifizieren und die Wirtsspezifität in Isolaten aus natürlichen Systemen in Frage zu stellen. In einer breiteren Perspektive betonte diese Arbeit die Notwendigkeit, Strategien bei der Erkennung, Quantifizierung und Identifizierung von Parasiten zu standardisieren und zu kombinieren, um ein besseres Verständnis auf evolutionärer und ökologischer Ebene zu erlangen. / This PhD thesis combines different approaches for parasite identification to assess the diversity of parasites in natural systems. Particularly, I focus on how species identification in the genus Eimeria is linked to its host specificity in rodent species. First, this thesis provides a set of methods to assess prevalence at the species level in Mus musculus systems. The approach integrates morphological description with molecular methods for detection, niche approximation and phylogenetic reconstruction. As a result, three different Eimeria species were identified, mice with double infections were detected and species-specific prevalence were predicted to be host density-dependent. For identification of Eimeria spp. across different host species, a novel high-throughput multi-locus genotyping was established and compared with single-marker genotyping. The multi-locus genotyping approach provided a higher resolution to distinguish closely related Eimeria isolates. This confirmed the species E. falciformis to have a single host species, the house mice. However, E. vermiformis and E. apionodes could not be distinguished suggesting a single species with broader host usage in a phylogenetic species concept. These findings show that the high host specificity traditionally assumed for Eimeria parasites is questionable, and that identification of species by host association should be avoided. The approaches for identification of Eimeria spp. Developed here allowed differentiation of closely related isolates with indistinguishable morphology. Molecular amplification, sequencing, genotyping and phylogeny allowed the identification of Eimeria at species level and to question host specificity in isolates from natural systems. In a broader perspective, this work emphasised the necessity to standardise and combine strategies in parasite detection, quantification and identification to gain better understanding at an evolutionary and ecological level.

Das tropische Südostasien, und besonders der Indo-Australische Archipel, ist bekannt für seine bemerkenswerte floristische und faunistische Diversität, besonders konzentriert in vier der identifizierten Biodiversitäts-Hotspots (Indochina, Sundaland, die Philippinen und Wallacea). In dieser Arbeit wird die biogeographische Geschichte Südostasiens beleuchtet, um Regionen mit einer erhöhten Biodiversität zu identifizieren und zu testen, ob dies mit Diversifikationen innerhalb der Region und Einwanderungen und/oder Auswanderungen korreliert und ob sich diese Faktoren über die Zeit hinweg ausgleichen. Ein besonderer Augenmerk wird auf Sulawesi und seine besondere Fauna gelegt, um zu testen, ob ein Ursprung durch Vikarianz für verschiedene Tiergruppen plausibel erscheint und wann Diversifikationen innerhalb der Fisch- und Schnecken-Radiationen im Malili-Seensystem begannen. Dabei wird auf Meta-Analysen und mehrere Disziplinen zurückgegriffen für eine integrative biogeographische Geschichte Südoastasiens und seiner Fauna, indem molekulare Uhr-Analysen, Berechnungen zur Ermittlung des Ursprungsortes mit tektonischen, paläogeographischen und klimatischen Rekonstruktionen verbunden werden, um potentielle Ursachen für die heutige Verbreitung zu finden. / Tropical Southeast Asia, and particularly the Indo-Australian Archipelago, is known for its tremendous floral and faunal biodiversity, mainly accumulated in four of the world’s biodiversity hotspots identified (Indochina, Sundaland, the Philippines, and Wallacea). Here, Southeast Asia’s biogeographic history is examined to identify areas being characterized by high levels of biodiversity (number of lineages, species richness) through time and to test whether the respective biota is mainly due to in situ diversification, immigration and/or emigration, or equilibrium dynamics. Moreover, this thesis focuses particularly on Sulawesi and its peculiar fauna to test if a vicariant origin appears plausible for certain groups and when the remarkable fish and snail radiations found in the Malili Lakes system started to diversify. To achieve this, meta-analytical and multi-disciplinary approaches are considered for an integrative historical biogeographic history of Southeast Asia and its biota by using molecular clock analyses and ancestral area estimations together with tectonic, palaeogeographic and climatic reconstructions to reveal potential causes for present-day distribution.