Characterization of P. vivax blood stage transcriptomes from field isolates reveals similarities among infections and complex gene isoforms

International audienceOur understanding of the structure and regulation of Plasmodium vivax genes is limited by our inability to grow the parasites in long-term in vitro cultures. Most P. vivax studies must therefore rely on patient samples, which typically display a low proportion of parasites and asynchronous parasites. Here, we present stranded RNA-seq data generated directly from a small volume of blood from three Cambodian vivax malaria patients collected before treatment. Our analyses show surprising similarities of the parasite gene expression patterns across infections, despite extensive variations in parasite stage proportion. These similarities contrast with the unique gene expression patterns observed in sporozoites isolated from salivary glands of infected Colombian mosquitoes. Our analyses also indicate that more than 10% of P. vivax genes encode multiple, often undescribed, protein-coding sequences, potentially increasing the diversity of proteins synthesized by blood stage parasites. These data also greatly improve the annotations of P. vivax gene untranslated regions, providing an important resource for future studies of specific genes. Plasmodium vivax is the second largest cause of human malaria around the world, accounting for about 8.5 million cases in 2015 and almost half of the reported malaria infections outside of sub-Saharan Africa 1. Most strategies deployed to eliminate malaria primarily target falciparum malaria and are less effective in controlling vivax malaria, the frequency of which is increasing in many endemic regions 2. Basic research on P. vivax has greatly fallen behind studies of P. falciparum due to a lack of continuous in vitro culture system. Studies of P. vivax often depend on clinical samples and are complicated by the parasite genetic diversity, the polyclonality of many infections, as well as the host genetic diversity and the confounding effects of previous exposures. Genomic techniques, including whole genome sequencing, have provided new tools for understanding P. vivax biology, but have so far only modestly improved our understanding of the biology of this pathogen 3–5. In particular, P. vivax genes are still incompletely annotated and the regulation of the parasite genes expressed, even during blood stage infections, remains poorly understood 2. Most studies of gene expression in Plasmodium parasites have been conducted using P. falciparum, due to its public health importance and its ability to be grown in vitro, which i) facilitates acquisition of study material , ii) enables synchronization of the parasite stages, and iii) provides a controlled (though artificial) environment. Fortunately, many of the observations initially made in P. falciparum have later been validated in other Plasmodium species 6. For example, the patterns of gene expression throughout the intraerythrocytic cycle o