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Genomic Determinants of Antigen Expression Hierarchy in African Trypanosomes
13 Mar 2025
A highly sensitive single-cell RNA sequencing approach sheds light on the VSG-selection mechanisms in Trypanosoma brucei.
Our PhD student Zhibek Keneskhanova and our postdoc Dr. Raúl Cosentino, together with Dr. Kirsty McWilliam (former postdoc), in collaboration with the Colomé-Tatché and Mugnier labs, have developed a high-resolution, trypanosome-adapted single-cell RNA sequencing method (Spliced-Leader Smart‑seq3xpress) to capture VSG switching events in Trypanosoma brucei. Their work addresses the long-standing question of why certain VSGs are activated more frequently than others. By inducing a double-strand break—a known trigger for VSG switching—in the active VSG gene, they demonstrate that both the availability of homologous repair templates and the genomic location of VSGs are critical determinants. When a homologous template is present, segmental gene conversion produces mosaic antigens; in its absence, break-induced replication activates a telomere-adjacent VSG. These findings establish a new genomic framework for understanding antigen switching and immune evasion in African trypanosomes.
Keneskhanova Z#, McWilliam KR#, Cosentino RO#, Barcons-Simon A, Dobrynin A, Smith JE, Subota I, Mugnier MR, Colomé-Tatché M*, Siegel TN * (2025)
Genomic determinants of antigen expression hierarchy in African trypanosomes.
Nature https://doi.org/10.1038/s41586-025-08720-w