Genomevolution und die Entstehung von piRNA-Clustern in Drosophila
Zusammenfassung der Projektergebnisse
This project investigates the relationship between transposable elements (TEs) and piRNA clusters in the context of genome evolution. TEs, known as ‘jumping genes’, can disrupt normal gene functions and threaten genome integrity. To counteract TEs in animal germlines, the PIWI/piRNA pathway has evolved, with piRNA clusters acting as 'master regulators' of TEs. However, our preliminary research challenged this model. In Drosophila melanogaster, the removal of three primary germline piRNA clusters did not lead to TE derepression, suggesting these clusters might be less essential for TE regulation than thought. Further, piRNA clusters were found to be evolutionarily transient and often emerged in unstable genomic locations. To expand on these findings, the project aims to: 1. Identify conditions for unstable genomic locations. 2. Study TE structure in emerging piRNA clusters. 3. Understand how unknown TEs are recognized without related piRNAs. Crucially, as the foundation of this project, the DFG fellowship allowed us to finalize and publish the work that gave rise to our further investigations. Subsequently, using HiC data and previously assembled nanopore-based genomes, we produced high-quality genome assemblies for 32 Drosophila species, which on its own represents a vast and valuable resource for research far beyond this project. This data, together with RNA-seq and small RNA-seq data, allowed in-depth analyses of the evolution of genomic rearrangements, TEs and the piRNA pathway, leading to significant insights into the dynamics of TE and piRNA cluster evolution. They revealed that genomic instability hotspots, three-dimensional genome structure, and proximity to pericentromeric regions influence the emergence of piRNA clusters. Moreover, these clusters have a species-specific but genome-typical TE content, further challenging the notion that they function as primary 'master regulators' of TEs. The acquired data is set to be published in multiple papers, including the description of a novel HiC scaffolding software developed due to inadequacies in the existing tools. For the analysis of piRNA clusters, we developed an annotation pipeline that was additionally used for construction of a large database that included overall 51 species from all major groups of metazoans, in a collaboration with researchers from Mainz (JGU) and Frankfurt (Senckenberg). Additionally, the project includes a study of the consequences and host reactions of a novel integration of the LTR-retrotransposon gypsy12 in D. melanogaster. While not finalized, this analysis serves as a foundation for future research within my own career development. Outside this main project, the DFG fellowship also enabled collaborations within our department on stem cell differentiation in Drosophila melanogaster and DNA methylation stability in TEs of mice, which strengthened my scientific network and familiarized me with novel techniques and research topics.
Projektbezogene Publikationen (Auswahl)
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Large Drosophila germline piRNA clusters are evolutionarily labile and dispensable for transposon regulation. Molecular Cell, 81(19), 3965-3978.e5.
Gebert, Daniel; Neubert, Lena K.; Lloyd, Catrin; Gui, Jinghua; Lehmann, Ruth & Teixeira, Felipe Karam
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piRNAclusterDB 2.0: update and expansion of the piRNA cluster database. Nucleic Acids Research, 50(D1), D259-D264.
Rosenkranz, David; Zischler, Hans & Gebert, Daniel
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Epigenetic inheritance is unfaithful at intermediately methylated CpG sites. Nature Communications, 14(1).
Hay, Amir D.; Kessler, Noah J.; Gebert, Daniel; Takahashi, Nozomi; Tavares, Hugo; Teixeira, Felipe K. & Ferguson-Smith, Anne C.
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Two distinct waves of transcriptome and translatome changes drive Drosophila germline stem cell differentiation. The EMBO Journal, 43(8), 1591-1617.
Samuels, Tamsin J.; Gui, Jinghua; Gebert, Daniel & Karam, Teixeira Felipe
