Abstract

BackgroundMalaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. Here we provide a high-resolution transcriptome of Plasmodium falciparum as it commits to and develops through gametocytogenesis.ResultsThe gametocyte-associated transcriptome is significantly different from that of the asexual parasites, with dynamic gene expression shifts characterizing early, intermediate and late-stage gametocyte development and results in differential timing for sex-specific transcripts. The transcriptional dynamics suggest strict transcriptional control during gametocytogenesis in P. falciparum, which we propose is mediated by putative regulators including epigenetic mechanisms (driving active repression of proliferation-associated processes) and a cascade-like expression of ApiAP2 transcription factors.ConclusionsThe gametocyte transcriptome serves as the blueprint for sexual differentiation and will be a rich resource for future functional studies on this critical stage of Plasmodium development, as the intraerythrocytic transcriptome has been for our understanding of the asexual cycle.

Highlights

  • Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood

  • We show that post-commitment, the gametocyte transcriptome correlates to specific epigenetic marks and Apicomplexan APetala 2 (ApiAP2) transcription factors

  • Expression values were captured for 96–99% of the 5443 genes on the array (P < 0.01, full dataset provided in Additional File 1), a 1.5-fold improvement in coverage compared to the 65% of the transcriptome (3410 genes) captured in the previously reported Young et al dataset [36]

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Summary

Introduction

Malaria pathogenesis relies on sexual gametocyte forms of the malaria parasite to be transmitted between the infected human and the mosquito host but the molecular mechanisms controlling gametocytogenesis remains poorly understood. The processes of asexual replication and sexual differentiation in Plasmodium are associated with distinct patterns of gene expression that are tightly controlled through complex regulatory systems [5]. These patterns have been investigated to some extent for asexual replication where P. falciparum parasites use both transcriptional [6,7,8] and post-transcriptional processes [9, 10] to effect a cascade of coordinated, stage-specific gene expression [11, 12]. Commitment to gametocytogenesis further requires stabilization of a subset of gametocyte-specific transcripts [18]

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