Comparative 3D Genome Organization in Apicomplexan Parasites

Evelien M. Bunnik1, Aarthi Venkat2,*, Jianlin Shao2,#,*, Kathryn E. McGovern3,$, Gayani Batugedara4, Danielle Worth3, Jacques Prudhomme4, Stacey A. Lapp5,6,7, Chiara Andolina8,% , Leila S. Ross9, Lauren Lawres10, Declan Brady11, Photini Sinnis12, Francois Nosten8, David A. Fidock9, Emma H. Wilson3, Rita Tewari11, Mary R. Galinski5,6,7, Choukri Ben Mamoun10, Ferhat Ay2,13,*, and Karine G. Le Roch4,* 2018.

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 P. vivax and P. berghei, and absent in P. yoelii. In P. 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.

Public datasets used and analyzed

B. microti reference genomes were procured from PiroplasmaDB, Plasmodium reference genomes from PlasmoDB, and T. gondii reference genomes from ToxoDB.

   Organism-Stage         FASTA         GFF       Gene Expression       Coordinates   
Bm mixed IDC   B. microti RI version 29      B. microti RI version 29       Silva, 2016    Centromeres       Virulence       Telomeres   
Bm tetrads   B. microti RI version 29      B. microti RI version 29       Silva, 2016    Centromeres       Virulence       Telomeres   
Pb gametocytes    P. berghei ANKA version 35      P. berghei ANKA version 35       Otto, 2014    Centromeres       Virulence       Telomeres   
Pf gametocytes    P. falciparum 3D7 version 28      P. falciparum 3D7 version 28       Bunnik, 2013    Centromeres       Virulence       Telomeres   
Pf sporozoites    P. falciparum 3D7 version 28      P. falciparum 3D7 version 28          Centromeres       Virulence       Telomeres   
Pf trophozoites    P. falciparum 3D7 version 28      P. falciparum 3D7 version 28       Bunnik, 2013    Centromeres       Virulence       Telomeres   
Pk trophozoites         PlasmoDB version 29       Hoo, 2016    Centromeres       Virulence       Telomeres   
Pv sporozoites    P. vivax Sal1 version 29      P. vivax Sal1 version 29       Westenberger, 2010    Centromeres       Virulence       Telomeres   
Py mixed IDC    P. yoelii 17X version 29      P. yoelii 17X version 29       Hoo, 2016    Centromeres       Virulence       Telomeres   
Tg bradyzoites    T. gondii ME49 version 29      T. gondii ME49 version 29       ToxoDB version 35    Centromeres       Virulence       Telomeres   
Tg tachyzoites    T. gondii ME49 version 29      T. gondii ME49 version 29       ToxoDB version 35    Centromeres       Virulence       Telomeres   

Data generated for this project

To replicate visualization of the figures in the paper, follow these instructions using the PDB files below.

   Organism         Hi-C heatmaps         3D Structures   
B. microti    Intrachr       Interchr       MixedBloodStagePDB       TetradsPDB   
P. berghei    Intrachr       Interchr       PDB   
P. falciparum    Intrachr       Interchr       GamPDB       SpzPDB       TrophPDB   
P. knowlesi    Intrachr       Interchr       PDB   
P. vivax    Intrachr       Interchr       PDB   
P. yoelii    Intrachr       Interchr       PDB   
T. gondii    Intrachr       Interchr       BradyPDB       TachyPDB   

Contact

For questions about the project and/or this supplementary page please e-mail Ferhat Ay.

Ferhat Ay < ferhatay at lji period org >