Comparative 3D genome organization in apicomplexan parasites

• Type of Material: Article
• Authors: Evelien M. Bunnik, University of Texas; Aarthi Venkat, La Jolla Institute for Immunology; Jianlin Shao, La Jolla Institute for Immunology; Kathryn E. McGovern, University of California Riverside; Gayani Batugedara, University of California Riverside; Danielle Worth, University of California Riverside; Jacques Prudhomme, University of California Riverside; Stacey A. Lapp, Emory University; Chiara Andolina, University of Oxford; Leila S. Ross, Columbia University; Lauren Lawres, Yale School of Medicine; Declan Brady, University of Nottingham; Photini Sinnis, Johns Hopkins University; Francois Nosten, University of Oxford; David A. Fidock, Columbia University; Emma H. Wilson, University of California Riverside; Rita Tewari, University of Nottingham; Mary Galinski, Emory University; Choukri Ben Ben Mamoun, Yale School of Medicine; Ferhat Ay, La Jolla Institute for Immunology; Karine G. Le Roch, University of California Riverside
• Language: English
• Date: 2019-02-19
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2019. Published under the PNAS license.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1810815116
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 0027-8424
• Volume: 116
• Issue: 8
• Start Page: 3183
• End Page: 3192
• Grant/Funding Information: This work was supported by NIH Grants R21 AI142506, R01 AI085077, R01 AI06775, and R01 AI136511 (to K.G.L.R.), R35 GM128938 (to F.A.), and R01 AI056840 (to P.S.); the NIAID/NIH Department of Health and Human Services (Contract HHSN272201200031C), which established the Malaria Host-Pathogen Interaction Center; the Office of Research Infrastructure Programs/Office of the Director Grant P51OD011132 (to M.R.G.); University of California, Riverside Grant NIFA-Hatch-225935 (to K.G.L.R.); Bill & Melinda Gates Foundation Grant OPP1040938 (to D.A.F.); Medical Research Council Grant MR/K011782/1 (to R.T.); and the University of Texas Health Science Center at San Antonio (E.M.B.).
• Keywords: PRINCIPLES; Science & Technology - Other Topics; genome organization; epigenomics; Hi-C; TOXOPLASMA-GONDII; ANTIGENIC VARIATION; FALCIPARUM; REVEALS; SEQUENCE; DIVERSITY; virulence; GENE-EXPRESSION; IMMUNITY; PLASMODIUM-KNOWLESI MALARIA; Multidisciplinary Sciences; malaria; Science & Technology

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 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.