Evolution & Development Group

Evolution of regulatory elements

Using a computational method developed in our lab, we identified phylogenetically conserved noncoding elements (PCNEs) in a manner that is not biased by rearrangement and duplication. We identified more than a thousand PCNEs that have been conserved between vertebrates and the basal chordate amphioxus. Via transgenic zebrafish assays we found that the majority of the computationally identified elements are functional enhancers. We could show that PCNEs are enriched around genes with ancient synteny conservation and that this association is strongest for extragenic PCNEs, suggesting that cis-regulatory interdigitation plays a key role in repressing genome rearrangement. Our results also demonstrate that subfunctionalization of conserved cis-regulation has not been the primary determinate of gene duplicate retention in vertebrates. Instead, the data supports the gene balance hypothesis, which proposes that duplicate retention has been driven by selection against dosage imbalances in genes with many protein connections.

New candidate autism susceptibility loci

In collaboration with the Clinic of Child Psychiatry of the University of Frankfurt (Prof. F. Poustka) and the German Cancer Research Center, Heidelberg (Dr. S. Klauck), we are carrying out whole genome and transcriptome sequencing of two multiplex autism families with at least two affected children and non affected parents and siblings. SNP analysis for the first family allowed us to identify a single de novo mutation in a gene of one of the patients that is likely to disrupt correct splicing of the corresponding transcript of an important regulatory protein, which is currently being analysed in cell-line assays. We anticipate enlarging this study and envision to setup an individualised diagnostics/treatment program for ASD in Germany

Zebrafish as model system to functionally analyse syntenic genes included in the human 16p11.2 ~600Kb region frequently deleted in autism patients

The tissue expression of nine zebrafish orthologs (kctd13, ASPHD1, DOC2A, ypel3, gdpd3, mapk3, ppp4ca, ppp4cb, aldoab, shank3b, arsa) of human genes located within the 16p11.2 region was analysed for six developmental stages between the gastrula (5.3-10hrs) and hatching (48-72 hrs) stages. Most of the genes are mainly expressed in neuronal tissues especially cerebellum, which is the brain region responsible for most of the functions that are affected in autistic patients.

Xenacoelomorpha: A new deuterostome Phylum

We have analysed three large datasets to investigate the phylogenetic position of Xenoturbella and Acoel worms: A) A complete set of mitochondrial genes from various acoels, nemertodermatids and Xenoturbella; B) A large phylogenomic data set of 38,330 aminoacid positions; and C) new micro RNA complements. Similar to previous studies, our phylogenomic analysis recovers a strong relation- ship between Xenoturbella and acoels, but shows also that the previous phyloge-

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