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

Evelien M Bunnik,Jean-Philippe Vert,Nelle Varoquaux,Photini Sinnis,William Stafford Noble,Declan Brady,Karine G Le Roch,Jacques Prudhomme,Francois Nosten,Chiara Andolina,Leila S Ross,Anthony Cort,Gayani Batugedara,Ferhat Ay,David A Fidock,Lirong Shi,Kate B Cook,Rita Tewari

doi:10.1038/s41467-018-04295-5

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.

Highlights

The development of malaria parasites throughout their various life cycle stages is coordinated by changes in gene expression
Several of these ApiAP2 transcription factors (TFs) are involved in stage transitions, such as PfAP2-G, which is thought to be the main driver for gametocyte differentiation[3,4,5]
To complement our previous study describing the genome architecture of P. falciparum during the intraerythrocytic developmental cycle (IDC)[16], we performed Hi-C experiments on three additional stages of the P. falciparum life cycle: early gametocytes, late gametocytes, and salivary gland sporozoites (Fig. 1a, Supplementary Table 1, and Supplementary Fig. 1) using the tethered conformation capture methodology

Summary

Introduction

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. Infection in humans starts when an infected female Anopheles mosquito takes a blood meal and transmits parasites that are present in the form of sporozoites in her salivary glands. A single family of ApiAP2 transcription factors (TFs) with 27 members has been identified, while approximately two-thirds of the TFs expected based on the size of the Plasmodium genome seem to be missing[2] Several of these ApiAP2 TFs are involved in stage transitions, such as PfAP2-G, which is thought to be the main driver for gametocyte differentiation[3,4,5]. Our understanding of how these TFs are controlled and how various TFs may act together to form transcriptional networks is still very limited

Methods

Results

Conclusion