Comparative 3D genome organization in apicomplexan parasites.

Abstract

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 <i>Plasmodium falciparum</i>, 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 <i>Plasmodium</i> species and two related apicomplexan parasites. <i>Plasmodium</i> species mainly showed clustering of centromeres, telomeres, and virulence genes. In <i>P. falciparum</i>, the heterochromatic virulence gene cluster had a strong repressive effect on the surrounding nuclear space, while this was less pronounced in <i>Plasmodium vivax</i> and <i>Plasmodium berghei</i>, and absent in <i>Plasmodium yoelii</i> In <i>Plasmodium knowlesi</i>, telomeres and virulence genes were more dispersed throughout the nucleus, but its 3D genome showed a strong correlation with gene expression. The <i>Babesia microti</i> genome showed a classical Rabl organization with colocalization of subtelomeric virulence genes, while the <i>Toxoplasma gondii</i> genome was dominated by clustering of the centromeres and lacked virulence gene clustering. Collectively, our results demonstrate that spatial genome organization in most <i>Plasmodium</i> species is constrained by the colocalization of virulence genes. <i>P. falciparum</i> and <i>P. knowlesi</i>, the only two <i>Plasmodium</i> 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.