Comparative 3D genome organization in apicomplexan parasites

Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):3183-3192. doi: 10.1073/pnas.1810815116. Epub 2019 Feb 5.


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

Keywords: Hi-C; epigenomics; genome organization; malaria; virulence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Centromere / genetics
  • Gene Expression Regulation / genetics
  • Genome, Protozoan / genetics*
  • Genomics
  • Heterochromatin / genetics*
  • Humans
  • Malaria, Falciparum / genetics*
  • Malaria, Falciparum / parasitology
  • Plasmodium berghei / genetics
  • Plasmodium berghei / pathogenicity
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / pathogenicity
  • Plasmodium knowlesi / genetics
  • Plasmodium knowlesi / pathogenicity
  • Plasmodium vivax / genetics
  • Plasmodium vivax / pathogenicity
  • Telomere / genetics
  • Toxoplasma / genetics
  • Toxoplasma / pathogenicity


  • Heterochromatin