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

Comparative 3D genome organization in apicomplexan parasites.

Author information

Department of Microbiology, Immunology & Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.
Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037.
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521.
Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521.
International Center for Malaria Research, Education and Development, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329.
Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA 30329.
Malaria Host-Pathogen Interaction Center, Emory University, Atlanta, GA 30329.
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, 63110 Tak, Thailand.
Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032.
Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520.
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom.
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037;
School of Medicine, University of California, San Diego, La Jolla, CA 92093.
Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521;


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.


Hi-C; epigenomics; genome organization; malaria; virulence

[Available on 2019-08-19]
[Indexed for MEDLINE]

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