Dynamic Simulation of active/inactive Chromatin Domains

In this thesis a new model is presented, which describes the formation of higher order chromatin structures with the help of polymer physics for the first time. It is a block-copolymer model for the compactification of the 30nm Chromatin fiber into higher order structures. The idea is that basically every condensing agent (HMG/SAR, HP1, cohesin, condensin, DNA-DNA interaction...) can be modelled as an effective attractive potential of specific chain segments. This way the formation of individual 1Mbp sized rosettes from a linear chain could be observed. Furthermore several Mbp of fiber were simulated, up to an entire chromosome and finally the entire nucleus of Drosophila Melanogaster. The simulation results were compared to experimental data and good agreement was found. The results have been published in the journals Eur. Biophys. J., Int. J. Mod. Phys. C, Int. J. Biol. Phys. and Biophys. Rev. Lett. A detailed list can be found in the appendix. Part of the computation was done on the IBM Blue Gene/L supercomputer at the Forschungszentrum Jülich

A Model for Segregation of Chromatin after Replication: Segregation of Identical Flexible Chains in Solution

We study the segregation of two long chains from parallel but randomly twisted start conformations under good solvent conditions using Monte Carlo simulations to mimic chromatin segregation after replication in eukaryotic cells in the end of prophase. To measure the segregation process, we consider the center-of-mass separation between the two chains and the average square distance between the monomers which were connected before segregation starts. We argue that segregation is dominated by free diffusion of the chains, assuming that untwisting can be achieved by Rouse-like fluctuations on the length scale of a twisted loop. Using scaling analysis, we find that chain dynamics is in very good agreement with the free diffusion hypothesis, and segregation dynamics follows this scaling nearly. Long chains, however, show retardation effects that can be described by a new (to us) dynamical exponent, which is slightly larger than the dynamical exponent for Rouse-like diffusion. Our results indicate that nearly free diffusion of chains during a timescale of a few Rouse-times can lead to segregation of chains. A main obstacle during segregation by free diffusion is random twists between daughter strands. We have calculated the number of twists formed by the daughter strands in the start conformations, which turns out to be rather low and increases only with the square-root of the chain length

Sunflower pan-genome analysis shows that hybridization altered gene content and disease resistance

International audienceDomesticated plants and animals often display dramatic responses to selection, but the origins of the genetic diversity underlying these responses remain poorly understood. Despite domestication and improvement bottlenecks, the cultivated sunflower remains highly variable genetically, possibly due to hybridization with wild relatives. To characterize genetic diversity in the sunflower and to quantify contributions from wild relatives, we sequenced 287 cultivated lines, 17 Native American landraces and 189 wild accessions representing 11 compatible wild species. Cultivar sequences failing to map to the sunflower reference were assembled de novo for each genotype to determine the gene repertoire, or 'pan-genome', of the cultivated sunflower. Assembled genes were then compared to the wild species to estimate origins. Results indicate that the cultivated sunflower pan-genome comprises 61,205 genes, of which 27% vary across genotypes. Approximately 10% of the cultivated sunflower pan-genome is derived through introgression from wild sunflower species, and 1.5% of genes originated solely through introgression. Gene ontology functional analyses further indicate that genes associated with biotic resistance are over-represented among introgressed regions, an observation consistent with breeding records. Analyses of allelic variation associated with downy mildew resistance provide an example in which such introgressions have contributed to resistance to a globally challenging disease