Genomic determinants of antigen expression hierarchy in African trypanosomes
Nature article from the Siegel lab, with first author IRTG member Zhibek Keneskhanova and collaboration with Maria Colomé-Tatché
12.03.2025
Zhibek Keneskhanova, Kirsty R. McWilliam, Raúl O. Cosentino, Anna Barcons-Simon, Atai Dobrynin, Jaclyn E. Smith, Ines Subota, Monica R. Mugnier, Maria Colomé-Tatché & T. Nicolai Siegel (2025) Genomic determinants of antigen expression hierarchy in African trypanosomes. Nature. https://doi.org/10.1038/s41586-025-08720-w
Abstract cited directly from the article:
Antigenic variation is an immune evasion strategy used by many different pathogens. It involves the periodic, non-random switch in the expression of different antigens throughout an infection. How the observed hierarchy in antigen expression is achieved has remained a mystery1,2. A key challenge in uncovering this process has been the inability to track transcriptome changes and potential genomic rearrangements in individual cells during a switch event. Here we report the establishment of a highly sensitive single-cell RNA sequencing approach for the model protozoan parasite Trypanosoma brucei. This approach has revealed genomic rearrangements that occur in individual cells during a switch event. Our data show that following a double-strand break in the transcribed antigen-coding gene—an important trigger for antigen switching—the type of repair mechanism and the resultant antigen expression depend on the availability of a homologous repair template in the genome. When such a template was available, repair proceeded through segmental gene conversion, creating new, mosaic antigen-coding genes. Conversely, in the absence of a suitable template, a telomere-adjacent antigen-coding gene from a different part of the genome was activated by break-induced replication. Our results show the critical role of repair sequence availability in the antigen selection mechanism. Furthermore, our study demonstrates the power of highly sensitive single-cell RNA sequencing methods in detecting genomic rearrangements that drive transcriptional changes at the single-cell level.
See BMC press release.
See LMU press release.