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<jats:p>The positioning of chromosomes in the nucleus of a eukaryotic cell is highly organized and has a complex and dynamic relationship with gene expression. In the human malaria parasite <jats:italic>Plasmodium falciparum</jats:italic>, the clustering of a family of virulence genes correlates with their coordinated silencing and has a strong influence on the overall organization of the genome. To identify conserved and species-specific principles of genome organization, we performed Hi-C experiments and generated 3D genome models for five <jats:italic>Plasmodium</jats:italic> species and two related apicomplexan parasites. <jats:italic>Plasmodium</jats:italic> species mainly showed clustering of centromeres, telomeres, and virulence genes. In <jats:italic>P. falciparum</jats:italic>, the heterochromatic virulence gene cluster had a strong repressive effect on the surrounding nuclear space, while this was less pronounced in <jats:italic>Plasmodium vivax</jats:italic> and <jats:italic>Plasmodium berghei</jats:italic>, and absent in <jats:italic>Plasmodium yoelii</jats:italic>. In <jats:italic>Plasmodium knowlesi</jats:italic>, telomeres and virulence genes were more dispersed throughout the nucleus, but its 3D genome showed a strong correlation with gene expression. The <jats:italic>Babesia microti</jats:italic> genome showed a classical Rabl organization with colocalization of subtelomeric virulence genes, while the <jats:italic>Toxoplasma gondii</jats:italic> genome was dominated by clustering of the centromeres and lacked virulence gene clustering. Collectively, our results demonstrate that spatial genome organization in most <jats:italic>Plasmodium</jats:italic> species is constrained by the colocalization of virulence genes. <jats:italic>P. falciparum</jats:italic> and <jats:italic>P. knowlesi</jats:italic>, the only two <jats:italic>Plasmodium</jats:italic> species with gene families involved in antigenic variation, are unique in the effect of these genes on chromosome folding, indicating a potential link between genome organization and gene expression in more virulent pathogens.</jats:p>

Original publication





Proceedings of the National Academy of Sciences


Proceedings of the National Academy of Sciences

Publication Date





3183 - 3192