Authors

K K Modrzynska¹; R S Kent¹; R Cameron¹; A P Waters¹; O B Billker²;  ¹ Wellcome Trust Centre for Molecular Parasitology,University of Glasgow;  ² Wellcome Trust Sanger Institute

Discussion

The transmission of malaria between the mammalian host and the mosquito vector relies on the subset of parasites which differentiate into male and female gametocytes. The earliest stages of this process, however, remain poorly understood, as the young gametocytes are morphologically indistinguishable from the asexual parasites and present at very low abundance within the infection. Recently, we described AP2-G - a transcription factor acting as a key regulator of gametocytogenesis across different Plasmodium species. AP2-G expression is well correlated with the percentage of gametocytes in the population and its deletion completely abolishes the gametocytogenesis.

Here we present the results of inducible overexpression of AP2-G in rodent malaria parasite Plasmodium berghei. Upon induction, the vast majority of parasites underwent synchronous differentiation into morphologically normal gametocytes with a normal male to female ratio. RNA-seq was used to generate a detailed timecourse of transcriptome changes throughout the gametocytogenesis. It revealed a small group of genes induced as early as 4h after the initiation of commitment, followed by subsequent waves of transcriptome modifications leading to a mature gametocyte RNA profile. Further analysis of these groups of genes provided new insights into the molecular mechanisms of gametocytogenesis, highlighting the relevance of additional apiAP2 transcription factors and RNA binding proteins in this process.