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, Anthony Cort, 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 () and Karine G. Le Roch ()
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Evelien M. Bunnik: The University of Texas Health Science Center at San Antonio
Kate B. Cook: University of Washington
Nelle Varoquaux: University of California
Gayani Batugedara: University of California Riverside
Jacques Prudhomme: University of California Riverside
Anthony Cort: University of California Riverside
Lirong Shi: Johns Hopkins Bloomberg School of Public Health
Chiara Andolina: University of Oxford, Old Road campus
Leila S. Ross: Columbia University Medical Center
Declan Brady: Queens Medical Centre, University of Nottingham
David A. Fidock: Columbia University Medical Center
Francois Nosten: University of Oxford, Old Road campus
Rita Tewari: Queens Medical Centre, University of Nottingham
Photini Sinnis: Johns Hopkins Bloomberg School of Public Health
Ferhat Ay: La Jolla Institute for Allergy & Immunology
Jean-Philippe Vert: MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology
William Stafford Noble: University of Washington
Karine G. Le Roch: University of California Riverside

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract The development of malaria parasites throughout their various life cycle stages is coordinated by changes in gene expression. We previously showed that the three-dimensional organization of the Plasmodium falciparum genome is strongly associated with gene expression during its replication cycle inside red blood cells. Here, we analyze genome organization in the P. falciparum and P. vivax transmission stages. Major changes occur in the localization and interactions of genes involved in pathogenesis and immune evasion, host cell invasion, sexual differentiation, and master regulation of gene expression. Furthermore, we observe 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. Our results suggest that the three-dimensional genome structure of human malaria parasites is strongly connected with transcriptional activity of specific gene families throughout the life cycle.

Date: 2018
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DOI: 10.1038/s41467-018-04295-5

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