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Lookup NU author(s): Dr Emma BriggsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The Trypanosoma brucei genome is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, hundreds of sub‑megabase chromosomes contain 177 bp repeats of unknown function, and VSG transcription sites localise to many telomeres. DNA replication dynamics have only been described in the megabase chromosome cores, and in the single active VSG transcription site. Using a Nanopore genome assembly, we show that megabase chromosome subtelomeres display a paucity of replication initiation events relative to the core, correlating with increased instability. In addition, replication of the active VSG transcription site is shown to originate from the telomere, likely causing targeted VSG recombination. Lastly, we provide evidence that the 177 bp repeats act as conserved DNA replication origins, explaining submegabase chromosome stability. Compartmentalized DNA replication therefore explains how T. brucei balances stable genome transmission with localised instability driving immune evasion.
Author(s): Krasilnikova M, Marques CA, Briggs EM, Lapsley C, Hamilton G, Beraldi D, Crouch K, McCulloch R
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2025
Volume: 16
Online publication date: 16/01/2025
Acceptance date: 07/01/2025
Date deposited: 09/04/2026
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-025-56087-3
DOI: 10.1038/s41467-025-56087-3
Data Access Statement: Nanopore and Illumina reads have been deposited to the NCBI Sequence Read Archive (SRA) under project number PRJNA962304. The assembled genome is available at the EMBO-EBI European nucleotide archive (ENA), accession number PRJEB75536. MFAseq sequencing data is available on the ENA under PRJEB11437. DRIP-seq and RNA-seq datasets are available under PRJEB21868. Source data are provided with this paper.
PubMed id: 39820334
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