SRA

Single-nucleotide variations (SNVs) in RNA, arising from co- and post-transcriptional phenomena including transcription errors and RNA-editing, are well studied in a range of organisms. In the malaria parasite Plasmodium falciparum, stage-specific and non-specific gene-expression variations accompany the parasite's array of developmental and morphological phenotypes over the course of its complex life cycle. However, the extent, rate and effect of sequence-level variation in the parasite's transcriptome are unknown. Here, we report the presence of pervasive, non-specific SNVs in the P. falciparum transcriptome. SNV rates for a gene were not correlated to the AT-content of that gene. Global SNV rates for the P. falciparum lines we used, and for publicly available P. vivax and P. falciparum clinical isolate datasets, were of the order of 10-3 per base, ~10x higher than rates we calculated for bacterial datasets. These variations may reflect an intrinsic transcriptional error rate in the parasite, and RNA editing may be responsible for a subset of them. This seemingly characteristic property of the parasite may have implications for clinical outcomes and the basic biology and evolution of P. falciparum and parasite biology more broadly, and we anticipate that our study will prompt further investigations into the exact sources, consequences and possible adaptive roles of these SNVs. Overall design: Variant-calling using REDItools 2.0 (https://github.com/tizianoflati/reditools2.0) done for 3 drug-resistant lines of P. falciparum; and also for a lab-adapted 3D7 line which was subjected separately to temperature stress and drug stress. Single-nucleotide variation rates were calculated from this data.