Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei
Abstract 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...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56087-3 |
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| author | Marija Krasiļņikova Catarina A. Marques Emma M. Briggs Craig Lapsley Graham Hamilton Dario Beraldi Kathryn Crouch Richard McCulloch |
| author_facet | Marija Krasiļņikova Catarina A. Marques Emma M. Briggs Craig Lapsley Graham Hamilton Dario Beraldi Kathryn Crouch Richard McCulloch |
| author_sort | Marija Krasiļņikova |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-19ebeb7ea7354fe3800c349009480b61 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-19ebeb7ea7354fe3800c349009480b612025-01-19T12:31:52ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-56087-3Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma bruceiMarija Krasiļņikova0Catarina A. Marques1Emma M. Briggs2Craig Lapsley3Graham Hamilton4Dario Beraldi5Kathryn Crouch6Richard McCulloch7University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University PlaceUniversity of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University PlaceUniversity of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University PlaceUniversity of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University PlaceMVLS Research Facilities, University of Glasgow, Wolfson Wohl Cancer Research Centre, Garscube Estate, Switchback Rd, BearsdenUniversity of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University PlaceUniversity of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University PlaceUniversity of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University PlaceAbstract 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.https://doi.org/10.1038/s41467-025-56087-3 |
| spellingShingle | Marija Krasiļņikova Catarina A. Marques Emma M. Briggs Craig Lapsley Graham Hamilton Dario Beraldi Kathryn Crouch Richard McCulloch Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei Nature Communications |
| title | Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei |
| title_full | Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei |
| title_fullStr | Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei |
| title_full_unstemmed | Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei |
| title_short | Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei |
| title_sort | nanopore sequencing reveals that dna replication compartmentalisation dictates genome stability and instability in trypanosoma brucei |
| url | https://doi.org/10.1038/s41467-025-56087-3 |
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