Integrated analysis of the Plasmodium species transcriptome

•Comparison of variations in mRNA abundance across six different Plasmodium species.•Transcriptional conservation and divergence of Plasmodium syntenic orthologs.•Pattern of Plasmodium transcriptome evolution are established.•Transcriptionally conserved orthologs represent attractive intervention targets.Malaria remains a major public health concern despite global efforts in the fight against this disease. The intraerythrocytic stage of the malaria parasites is currently in the spotlight for anti-malarial intervention and vaccine targets. The primary goal of this study is to generate a comprehensive and directly comparable transcriptome dataset across multiple Plasmodium species originating from different hosts. We establish that specific pathways and intraerythrocytic stages are more transcriptionally diverged than others, reflecting transcriptional evolutionary diversity. We further propose a panel of transcriptionally conserved genes as potential drug targets.

The genome sequence available for different Plasmodium species is a valuable resource for understanding malaria parasite biology. However, comparative genomics on its own cannot fully explain all the species-specific differences which suggests that other genomic aspects such as regulation of gene expression play an important role in defining species-specific characteristics. Here, we developed a comprehensive approach to measure transcriptional changes of the evolutionary conserved syntenic orthologs during the intraerythrocytic developmental cycle across six Plasmodium species. We show significant transcriptional constraint at the mid-developmental stage of Plasmodium species while the earliest stages of parasite development display the greatest transcriptional variation associated with critical functional processes. Modeling of the evolutionary relationship based on changes in transcriptional profile reveal a phylogeny pattern of the Plasmodium species that strictly follows its mammalian hosts. In addition, the work shows that transcriptional conserved orthologs represent potential future targets for anti-malaria intervention as they would be expected to carry out key essential functions within the parasites. This work provides an integrated analysis of orthologous transcriptome, which aims to provide insights into the Plasmodium evolution thereby establishing a framework to explore complex pathways and drug discovery in Plasmodium species with broad host range.