Exceptionally high sequence-level variation in the transcriptome of Plasmodium falciparum

Single-nucleotide variations in RNA (hereafter referred to simply as SNVs), arising from co- and post-transcriptional phenomena including transcription errors and RNA editing, are well studied in organisms ranging from bacteria to humans. In the malaria parasite Plasmodium falciparum, stage-specific and non-specific gene-expression variations are known to accompany the parasites 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 parasites transcriptome are unknown. Here, we report the presence of pervasive, non-specific SNVs in the transcriptome of the P. falciparum. We show that these SNVs cover most of the parasites transcriptome. SNV rates for the P. falciparum lines we assayed, as well as for publicly available P. vivax and P. falciparum clinical isolate datasets were of the order of 10-3 per base, about tenfold higher than rates we calculated for bacterial datasets. These SNVs 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.