@article{HilgersHartmannHofreiteretal.2018,
  author    = {Hilgers, Leon and Hartmann, Stefanie and Hofreiter, Michael and von Rintelen, Thomas},
  title     = {Novel Genes, Ancient Genes, and Gene Co-Option Contributed o the Genetic Basis of the Radula, a Molluscan Innovation},
  series = {Molecular biology and evolution},
  volume    = {35},
  journal   = {Molecular biology and evolution},
  number    = {7},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0737-4038},
  doi       = {10.1093/molbev/msy052},
  pages     = {1638 -- 1652},
  year      = {2018},
  abstract  = {The radula is the central foraging organ and apomorphy of the Mollusca. However, in contrast to other innovations, including the mollusk shell, genetic underpinnings of radula formation remain virtually unknown. Here, we present the first radula formative tissue transcriptome using the viviparous freshwater snail Tylomelania sarasinorum and compare it to foot tissue and the shell-building mantle of the same species. We combine differential expression, functional enrichment, and phylostratigraphic analyses to identify both specific and shared genetic underpinnings of the three tissues as well as their dominant functions and evolutionary origins. Gene expression of radula formative tissue is very distinct, but nevertheless more similar to mantle than to foot. Generally, the genetic bases of both radula and shell formation were shaped by novel orchestration of preexisting genes and continuous evolution of novel genes. A significantly increased proportion of radula-specific genes originated since the origin of stem-mollusks, indicating that novel genes were especially important for radula evolution. Genes with radula-specific expression in our study are frequently also expressed during the formation of other lophotrochozoan hard structures, like chaetae (hes1, arx), spicules (gbx), and shells of mollusks (gbx, heph) and brachiopods (heph), suggesting gene co-option for hard structure formation. Finally, a Lophotrochozoa-specific chitin synthase with a myosin motor domain (CS-MD), which is expressed during mollusk and brachiopod shell formation, had radula-specific expression in our study. CS-MD potentially facilitated the construction of complex chitinous structures and points at the potential of molecular novelties to promote the evolution of different morphological innovations.},
  language  = {en}
}
@article{HilgersHartmannPfaenderetal.2022,
  author    = {Hilgers, Leon and Hartmann, Stefanie and Pfaender, Jobst and Lentge-Maass, Nora and Marwoto, Ristiyanti M. and von Rintelen, Thomas and Hofreiter, Michael},
  title     = {Evolutionary divergence and radula diversification in two ecomorphs from an adaptive radiation of freshwater snails},
  series = {Genes},
  volume    = {13},
  journal   = {Genes},
  number    = {6},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2073-4425},
  doi       = {10.3390/genes13061029},
  pages     = {16},
  year      = {2022},
  abstract  = {(1) Background: Adaptive diversification of complex traits plays a pivotal role in the evolution of organismal diversity. In the freshwater snail genus Tylomelania, adaptive radiations were likely promoted by trophic specialization via diversification of their key foraging organ, the radula. (2) Methods: To investigate the molecular basis of radula diversification and its contribution to lineage divergence, we used tissue-specific transcriptomes of two sympatric Tylomelania sarasinorum ecomorphs. (3) Results: We show that ecomorphs are genetically divergent lineages with habitat-correlated abundances. Sequence divergence and the proportion of highly differentially expressed genes are significantly higher between radula transcriptomes compared to the mantle and foot. However, the same is not true when all differentially expressed genes or only non-synonymous SNPs are considered. Finally, putative homologs of some candidate genes for radula diversification (hh, arx, gbb) were also found to contribute to trophic specialization in cichlids and Darwin's finches. (4) Conclusions: Our results are in line with diversifying selection on the radula driving Tylomelania ecomorph divergence and indicate that some molecular pathways may be especially prone to adaptive diversification, even across phylogenetically distant animal groups.},
  language  = {en}
}
@misc{PerscheidFaberKrausetal.2018,
  author    = {Perscheid, Cindy and Faber, Lukas and Kraus, Milena and Arndt, Paul and Janke, Michael and Rehfeldt, Sebastian and Schubotz, Antje and Slosarek, Tamara and Uflacker, Matthias},
  title     = {A tissue-aware gene selection approach for analyzing multi-tissue gene expression data},
  series = {2018 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)},
  journal   = {2018 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)},
  publisher = {IEEE},
  address   = {New York},
  isbn      = {978-1-5386-5488-0},
  issn      = {2156-1125},
  doi       = {10.1109/BIBM.2018.8621189},
  pages     = {2159 -- 2166},
  year      = {2018},
  abstract  = {High-throughput RNA sequencing (RNAseq) produces large data sets containing expression levels of thousands of genes. The analysis of RNAseq data leads to a better understanding of gene functions and interactions, which eventually helps to study diseases like cancer and develop effective treatments. Large-scale RNAseq expression studies on cancer comprise samples from multiple cancer types and aim to identify their distinct molecular characteristics. Analyzing samples from different cancer types implies analyzing samples from different tissue origin. Such multi-tissue RNAseq data sets require a meaningful analysis that accounts for the inherent tissue-related bias: The identified characteristics must not originate from the differences in tissue types, but from the actual differences in cancer types. However, current analysis procedures do not incorporate that aspect. As a result, we propose to integrate a tissue-awareness into the analysis of multi-tissue RNAseq data. We introduce an extension for gene selection that provides a tissue-wise context for every gene and can be flexibly combined with any existing gene selection approach. We suggest to expand conventional evaluation by additional metrics that are sensitive to the tissue-related bias. Evaluations show that especially low complexity gene selection approaches profit from introducing tissue-awareness.},
  language  = {en}
}
@phdthesis{Saussenthaler2021,
  author    = {Saussenthaler, Sophie},
  title     = {The impact of DNA methylation on susceptibility to typ 2 diabetes in NZO mice},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XIX, 150},
  year      = {2021},
  abstract  = {The development of type 2 diabetes (T2D) is driven by genetic as well as life style factors. However, even genetically identical female NZO mice on a high-fat diet show a broad variation in T2D onset. The main objective of this study was to elucidate and investigate early epigenetic determinants of type 2 diabetes. Prior to other experiments, early fat content of the liver (<55.2 HU) in combination with blood glucose concentrations (>8.8 mM) were evaluated as best predictors of diabetes in NZO females. Then, DNA methylome and transcriptome were profiled to identify molecular pathophysiological changes in the liver before diabetes onset. The major finding of this thesis is that alterations in the hepatic DNA methylome precede diabetes onset. Of particular interest were 702 differentially methylated regions (DMRs), of which 506 DMRs had genic localization. These inter-individual DMRs were enriched by fivefold in the KEGG pathway type 2 diabetes mellitus, independent of the level of gene expression, demonstrating an epigenetic predisposition toward diabetes. Interestingly, among the list of hepatic DMRs, eleven DMRs were associated with known imprinted genes in the mouse genome. Thereby, six DMRs (Nap1l5, Mest, Plagl1, Gnas, Grb10 and Slc38a4) localized to imprinting control regions, including five iDMRs that exhibited hypermethylation in livers of diabetes-prone mice. This suggests that gain of DNA methylation in multiple loci of the paternal alleles has unfavourable metabolic consequences for the offspring. Further, the comparative liver transcriptome analysis demonstrated differences in expression levels of 1492 genes related to metabolically relevant pathways, such as citrate cycle and fatty acid metabolism. The integration of hepatic transcriptome and DNA methylome indicated that 449 differentially expressed genes were potentially regulated by DNA methylation, including genes implicated in insulin signaling. In addition, liver transcriptomic profiling of diabetes-resistant and diabetes-prone mice revealed a potential transcriptional dysregulation of 17 hepatokines, in particular Hamp. The hepatic expression of Hamp was decreased by 52\% in diabetes-prone mice, on account of an increase in DNA methylation of promoter CpG-118. Hence, HAMP protein levels were lower in mice prone to develop diabetes, which correlated to higher liver triglyceride levels.. In sum, the identified DNA methylation changes appear to collectively favor the initiation and progression of diabetes in female NZO mice. In near future, epigenetic biomarkers are likely to contribute to improved diagnosis for T2D.},
  language  = {en}
}