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

疟原虫传播阶段寄生虫特异性基因家族基因组组织的变化

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作者: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, Karine G Le Roch

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.

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