@article{a1b67eab725946ebbddad9824521ca87,
title = "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 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 = "Epigenomics, Genome organization, Hi-C, Malaria, Virulence",
author = "Bunnik, {Evelien M.} and Aarthi Venkat and Jianlin Shao and McGovern, {Kathryn E.} and Gayani Batugedara and Danielle Worth and Jacques Prudhomme and Lapp, {Stacey A.} and Chiara Andolina and Ross, {Leila S.} and Lauren Lawres and Declan Brady and Photini Sinnis and Francois Nosten and Fidock, {David A.} and Wilson, {Emma H.} and Rita Tewari and Galinski, {Mary R.} and Mamoun, {Choukri Ben} and Ferhat Ay and {Le Roch}, {Karine G.}",
note = "Funding Information: We thank Nelle Varoquaux (University of California, Berkeley) for help with generating 3D genome models; Kate Cook (University of Washington, Seattle) for help with implementation of the misassembly metrics; Clay Clark, John Weger, and Glenn Hicks (Institute for Integrative Genome Biology, University of California, Riverside) for their assistance in Illumina sequencing; the Insectary and Parasitology Core Facilities at the Johns Hopkins Malaria Research Institute, in particular Abai Tripathi, Godfree Mlambo, and Chris Kizito for their outstanding work; and The Bloomberg Family Foundation for supporting these facilities. Shoklo Malaria Research Unit is part of the Mahidol-Oxford University Research Unit, supported by the Wellcome Trust. The following reagent was obtained through the MR4 as part of the BEI Resources Repository, National Institute of Allergy and Infectious Diseases (NIAID), NIH: NF54 (MRA-1000), deposited by Megan Dowler, Walter Reed Army Institute of Research. 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.). Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All Rights Reserved.",
year = "2019",
month = feb,
day = "19",
doi = "10.1073/pnas.1810815116",
language = "English (US)",
volume = "116",
pages = "3183--3192",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "8",
}