Dokument: Intra-strain genetic heterogeneity in Toxoplasma gondii ME49: Oxford Nanopore long-read sequencing reveals copy number variation in the ROP8-ROP2A locus

Titel:Intra-strain genetic heterogeneity in Toxoplasma gondii ME49: Oxford Nanopore long-read sequencing reveals copy number variation in the ROP8-ROP2A locus
URL für Lesezeichen:https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=72011
URN (NBN):urn:nbn:de:hbz:061-20260123-124032-1
Kollektion:Publikationen
Sprache:Englisch
Dokumententyp:Wissenschaftliche Texte » Artikel, Aufsatz
Medientyp:Text
Autoren: Gohar, Yomna [Autor]
Neumann, Marie [Autor]
Hülse, Lisanna [Autor]
Wind, Daniel [Autor]
Mock, Julia [Autor]
Buchholz, Karin [Autor]
Helle, Marcel [Autor]
Sorg, Ursula R. [Autor]
Degrandi, Daniel [Autor]
Pfeffer, Klaus Dieter [Autor]
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Dateien vom 23.01.2026 / geändert 23.01.2026
Stichwörter:Within-strain variation , Toxoplasma gondii , Structural variation, Genome assembly , Oxford nanopore long-read sequencing
Beschreibung:Background

Toxoplasma gondii is an important pathogen and model organism for studying mechanisms of immune evasion and defense. Within the same strain, model organisms are typically assumed to be isogenic; for T. gondii, within-strain genetic divergence has been detected based on phenotypic changes and older molecular techniques but not characterized at the genomic level. We therefore used Oxford Nanopore long-read sequencing to characterize three independently maintained T. gondii ME49 isolates: 2015T and 2020T (obtained from ATCC and propagated in cell culture), and 2000B (propagated in mice).
Results

We de novo assembled a new T. gondii ME49 reference genome and, using state-of-the-art variant calling combined with pangenomic genotyping, detected variants between the sequenced isolates. Our new reference genome exceeded existing reference genomes in continuity (NG50 = 6.68 Mb versus 1.2 Mb in RefSeq) and structural accuracy, resolving all chromosomes except for a single break in the ribosomal DNA region. For isolates 2000B and 2020T, we identified 106 and 128 variants, respectively, across a final call set of 79 SNVs, 93 INDELs, and five structural variants; 18 small non-synonymous variants included genes associated with T. gondii life cycle (AP2X-8) and virulence in vivo (6-phosphogluconate dehydrogenase). A 13 kb expansion in the ROP8-ROP2A virulence locus increased the copy number of ROP2A-ROP8 genes in isolates 2000B and 2020T from three to six.
Conclusions

We provide an improved T. gondii ME49 reference genome and demonstrate the potentially confounding effect of intra-strain genetic heterogeneity, highlighting the need for continuous genomic monitoring for long-term genetic identity.
Rechtliche Vermerke:Originalveröffentlichung:
Gohar, Y., Neumann, M., Hülse, L., Wind, D., Mock, J., Buchholz, K., Helle, M., Sorg, U. R., Degrandi, D., Pfeffer, K. D., & Dilthey, A. (2025). Intra-strain genetic heterogeneity in Toxoplasma gondii ME49: Oxford Nanopore long-read sequencing reveals copy number variation in the ROP8-ROP2A locus. BMC Genomics, 26(1), Article 1094. https://doi.org/10.1186/s12864-025-12372-5
Lizenz:Creative Commons Lizenzvertrag
Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz
Fachbereich / Einrichtung:Medizinische Fakultät
Dokument erstellt am:23.01.2026
Dateien geändert am:23.01.2026
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