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LINUX Cluster Project

Nutzung der Internet-Dienste


  • Name: Fakultät für Biologie, Biozentrum, LMU
  • Address: Großhaderner Str. 2, 82152 Planegg-Martinsried
  • Project Proposal Date: 2017-11-20 11:36:43


1.The biggest challenge when undertaking a quest for traces of selective events in molecular variation data is the stochastic noise arising from the interplay between genetic drift and the demographic events that the studied populations underwent. Among those demographic events, fluctuations in population sizes due to founder events (i.e. bottlenecks) can potentially create an important variance in the time to the most recent common ancestor of a sample of genes along a chromosome. When this is the case, it becomes impossible to simply rely on the assumption that selection leaves local genetic footprints whereas demography affects the whole genome. Indeed, demography does affect genetic variation along the whole genome, but in a stochastic manner which means that it will create several local deviations to neutrality that might then be misinterpreted as signatures of selection. Because of this serious problem, most of the selection-detection methods rely somehow on the users knowledge of the demographical history of his species. This project aims to provide an accurate estimation of the demography of three Drosophila melanogaster worldwide populations. This will be done by conducting an approximate bayesian computation analysis (ABC). The results of this projects will be an essential pre-requisite for projects aiming at detecting footprints of natural selection in genetic polymorphism variation data. 2.Wild tomato species, which originated in western South America and the Galapagos Islands, are found in a wide range of habitats, and have thus to cope with various abiotic (e.g. temperature fluctuations, drought) and biotic stresses (e.g. attack by pathogens and herbivores). In order to study the genetic basis of such adaptations, we pursue the following specific aims: First, we derive new methods for estimating parameters of the speciation process, namely recurrent gene flow between the incipient species, taking into account the specific metapopulation structure of wild tomato species. Second, we develop methods to study in detail the population history of the tomato species, including seed banks, population subdivision, and population size expansion. The results of these studies are key theoretical requirements for detecting selection in genes underlying adaptation in tomatoes. 3.The rapid progress in genetic screening assays and DNA sequencing techniques promises to increase our understanding of the complex relationship between the human genetic make-up (the genotype) and its associated traits (the phenotype). We will make use of simulated data. For example, using the composite human genome sequences genome-wide association studies have identified regions that control specific traits through single nucleotide polymorphisms (SNPs) � the most common form of genetic variation. 4.We are interested to study the statistical distribution and the kinetics of nuclear proteins in respect to the nuclear architecture. Using Monte-Carlo simulation we combine Brownian motion with binding rates. Particles diffuse and bind at random while they are tracked when going through the focal volume. By this means simulations can be compared with single particle tracking data. 5.Wir entwickeln Bayessche und Maximum-Likelihood-basierte Methoden zur Analyse positiver Selektion in divergierenden Populationen, die demographischen Prozessen unterliegen, insbesondere rezenter Artbildung, Introgression, Substruktur in den Populationen und zeitlichen Änderungen von Populationsgrößen. In unserem zweistufigen Verfahren untersuchen wir zunächst diese Prozesse anhand von Sequenzdaten von neutral evolvierenden Loci. Die Ergebnisse verwenden wir dann zur Analyse von Genen, die mit evolutionären Anpassungsprozessen in Verbindung gebracht werden. Dabei kombinieren wir neue Summary-Statistiken, die auf Frequenzspektren von Polymorphismen basieren, mit Markoffketten-Monte-Carlo-Techniken. Einige der verwendeten Summary-Statisitiken entwerfen wir speziell zur Unterscheidung zwischen positiv gerichteter und balancierender/diversifizierender Selektion. Wir untersuchen mit diesen Methoden Datensätze aus verschiedenen Projekten. Unser primäres Anwendungsbeispiel ist ein Datensatz von 17 Loci aus zwei Wildtomatenarten, die Flusstäler an den Westabhängen der Anden besiedeln. Dadurch sind beide Arten in geographisch isolierte Subpopulationen unterteilt. Dies könnte einerseits die Ausbreitung selektiv vorteilhafter Substitutionen behindern und andererseits lokale Anpassung erleichtern. 6.An einer lückenlosen Ultradünnschnittserie (ca. 300 Schnitte) durch die OPL (outer plexiform layer) der Retina der Europäischen Sardelle (Engraulis encrasicolus) sollen die synaptischen Strukturen der Photorezeptoren und ihre Verschaltung mit den Sekundärneuronen untersucht und drei-dimensional dargestellt werden, um die neuronalen Verschaltungsregeln einer spezialisierten Vertebratenretina aufzudecken und zu verstehen. Für eine sinnvolle Strukturanalyse ist die Untersuchung eines größeren Areals von ca. 5x5 Zapfensynapsen notwendig, da sich die dendritischen Felder der Sekundärneuronen weit verzweigen. Hierfür wurden mehrere hochauflösende TEM-Teilbilder (Pixelgröße ca. 3x3 nm) jeden Schnittes erstellt und mittels Photoshop CS zu einem Bild zusammengefügt. 7.Previous studies have shown that splicing efficiency, and thus maturation of pre-mRNA, depends on the correct folding of the RNA molecule into a secondary- or higher-order structure. When disrupted by a mutation, aberrant folding may result in a lower splicing efficiency. However, the structure can be restored by a second, compensatory mutation. Under the influence of various evolutionary forces such as mutation and selection, a local secondary structure element (helix) will accumulate these nucleotide double-substitutions (covariations). The chance of a substitution and thus the rate of evolution depends on different properties of the helix. We developed a logistic regression approach to analyze the evolutionary dynamics of RNA secondary structures. We apply our approach to a set of computationally predicted RNA secondary structures in vertebrate introns. Our results are consistent with the hypothesis of a negative influence of the physical distance between pairing nucleotides on the occurrence of covariations, as predicted by Kimura?s model of compensatory evolution. We also confirm the hypothesis that longer helices can accommodate a larger number of covariations, wobbles (GU basepairs) and mis- matches. Furthermore, we find that wobbles and mismatches are more frequent in the middle of a helix, whereas covariations occur preferentially at the helix ends. The GC content is a major determinant of this pattern. In addition we performed a simulation study to detect putative biases in the secondary structure prediction. It suggests that the observed estimates are rather conservative. With the logistic regression framework developed here, we are able to establish a null model for the evolution of a helix and gain new insights into the evolutionary dynamics of compensation by double mutations. However, it is also important to test the selective constraints on RNA secondary structures in general. Therefore a further evaluation of nucleotide substitution rates in these structures has to be conducted. We are identifying quantitative trait loci (QTL) that contribute to temperature adaptation in Drosophila melanogaster. These QTL are directly associated with the species' successful colonization of contrasting environments on earth. We also plan to dissect some of these QTL to find the causative genes affecting the trait, and using population genetics methods I will study the evolutionary forces that maintain genetic variability at these genes. We are going to quantify the relative contributions of various forms of natural selection (including positive directional, balancing, and stabilizing selection)