The genetic landscape of origins of replication in <i>P. falciparum</i> - Archive ouverte HAL
Article Dans Une Revue Nucleic Acids Research Année : 2023

The genetic landscape of origins of replication in P. falciparum

Casilda Muñoz Castellano
  • Fonction : Auteur
Laurent Lacroix
Emilie Mathis
  • Fonction : Auteur
Paulina Prorok
  • Fonction : Auteur
Magali Hennion
Jose-Juan Lopez-Rubio
  • Fonction : Auteur
Marcel Méchali
  • Fonction : Auteur
Ana Rita Gomes
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Résumé

Abstract Various origin mapping approaches have enabled genome-wide identification of origins of replication (ORI) in model organisms, but only a few studies have focused on divergent organisms. By employing three complementary approaches we provide a high-resolution map of ORIs in Plasmodium falciparum, the deadliest human malaria parasite. We profiled the distribution of origin of recognition complex (ORC) binding sites by ChIP-seq of two PfORC subunits and mapped active ORIs using NFS and SNS-seq. We show that ORIs lack sequence specificity but are not randomly distributed, and group in clusters. Licensing is biased towards regions of higher GC content and associated with G-quadruplex forming sequences (G4FS). While strong transcription likely enhances firing, active origins are depleted from transcription start sites. Instead, most accumulate in transcriptionally active gene bodies. Single molecule analysis of nanopore reads containing multiple initiation events, which could have only come from individual nuclei, showed a relationship between the replication fork pace and the distance to the nearest origin. While some similarities were drawn with the canonic eukaryote model, the distribution of ORIs in P. falciparum is likely shaped by unique genomic features such as extreme AT-richness—a product of evolutionary pressure imposed by the parasitic lifestyle.
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Dates et versions

hal-04535862 , version 1 (07-04-2024)

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Casilda Muñoz Castellano, Laurent Lacroix, Emilie Mathis, Paulina Prorok, Magali Hennion, et al.. The genetic landscape of origins of replication in P. falciparum. Nucleic Acids Research, 2023, 52 (2), pp.660 - 676. ⟨10.1093/nar/gkad1103⟩. ⟨hal-04535862⟩
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