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Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages

View ORCID ProfileEvelien M. Bunnik, View ORCID ProfileKate B. Cook, Nelle Varoquaux, Gayani Batugedara, Jacques Prudhomme, Lirong Shi, Chiara Andolina, Leila S. Ross, Declan Brady, David A. Fidock, Francois Nosten, Rita Tewari, Photini Sinnis, View ORCID ProfileFerhat Ay, View ORCID ProfileJean-Philippe Vert, View ORCID ProfileWilliam Stafford Noble, Karine G. Le Roch
doi: https://doi.org/10.1101/242123
Evelien M. Bunnik
1Department of Microbiology, Immunology & Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
2Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, CA 92521, USA
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Kate B. Cook
3Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
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  • For correspondence: william-noble@uw.edu karine.leroch@ucr.edu
Nelle Varoquaux
4Department of Statistics, University of California, Berkeley, CA 94720, USA
5Berkeley Institute for Data Science, Berkeley, CA 94720, USA
6MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Fontainebleau, F-77300, France
7Institut Curie, Paris, F-75248, France
8U900, INSERM, Paris, F-75248, France
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Gayani Batugedara
2Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, CA 92521, USA
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Jacques Prudhomme
2Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, CA 92521, USA
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Lirong Shi
9Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
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Chiara Andolina
10Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Tak 63110, Thailand
11Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research building, University of Oxford, Oxford, OX3 7FZ, UK
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Leila S. Ross
12Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA
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Declan Brady
13School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK
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David A. Fidock
12Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA
14Division of Infectious Diseases, Department of Medicine, Columbia University, New York, NY 10032, USA
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Francois Nosten
10Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Tak 63110, Thailand
11Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research building, University of Oxford, Oxford, OX3 7FZ, UK
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Rita Tewari
13School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK
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Photini Sinnis
9Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
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Ferhat Ay
15La Jolla Institute for Allergy & Immunology, La Jolla, CA 92037, USA
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Jean-Philippe Vert
6MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, Fontainebleau, F-77300, France
7Institut Curie, Paris, F-75248, France
8U900, INSERM, Paris, F-75248, France
16Département de mathématiques et applications, École normale supérieure, CNRS, PSL Research University, 75005 Paris, France
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William Stafford Noble
3Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
17Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA
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  • For correspondence: william-noble@uw.edu karine.leroch@ucr.edu
Karine G. Le Roch
2Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, CA 92521, USA
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  • For correspondence: william-noble@uw.edu karine.leroch@ucr.edu
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ABSTRACT

The development of malaria parasites throughout their various life cycle stages is controlled by coordinated changes in gene expression. We previously showed that the three-dimensional organization of the P. falciparum genome is strongly associated with gene expression during its replication cycle inside red blood cells. Here, we analyzed genome organization in the P. falciparum and P. vivax transmission stages. Major changes occurred in the localization and interactions of genes involved in pathogenesis and immune evasion, erythrocyte and liver cell invasion, sexual differentiation and master regulation of gene expression. In addition, we observed reorganization of subtelomeric heterochromatin around genes involved in host cell remodeling. Depletion of heterochromatin protein 1 (PfHP1) resulted in loss of interactions between virulence genes, confirming that PfHP1 is essential for maintenance of the repressive center. Overall, our results suggest that the three-dimensional genome structure is strongly connected with transcriptional activity of specific gene families throughout the life cycle of human malaria parasites.

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Posted January 03, 2018.
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Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages
Evelien M. Bunnik, Kate B. Cook, Nelle Varoquaux, Gayani Batugedara, Jacques Prudhomme, Lirong Shi, Chiara Andolina, Leila S. Ross, Declan Brady, David A. Fidock, Francois Nosten, Rita Tewari, Photini Sinnis, Ferhat Ay, Jean-Philippe Vert, William Stafford Noble, Karine G. Le Roch
bioRxiv 242123; doi: https://doi.org/10.1101/242123
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Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages
Evelien M. Bunnik, Kate B. Cook, Nelle Varoquaux, Gayani Batugedara, Jacques Prudhomme, Lirong Shi, Chiara Andolina, Leila S. Ross, Declan Brady, David A. Fidock, Francois Nosten, Rita Tewari, Photini Sinnis, Ferhat Ay, Jean-Philippe Vert, William Stafford Noble, Karine G. Le Roch
bioRxiv 242123; doi: https://doi.org/10.1101/242123

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