Investigating the Occurrence and Extent of Single Nucleotide Variations in the Transcriptome of the Malaria Parasite Plasmodium falciparum.

Abstract

Single-nucleotide variations in RNA (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 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. In this work, we report the presence of pervasive, non-specific SNVs in the transcriptome of the P. falciparum. We use RNA sequencing data in combination with whole-genome sequencing data in order to accurately and empirically report these SNVs and exclude transcriptional variations passed down from genomic variants and show that these SNVs cover most of the parasite’s transcriptome. SNV rates for the P. falciparum lines we assayed, as well as those for publicly available P. vivax and P. falciparum 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. We anticipate that our study will prompt further investigations into the exact sources, consequences and possible adaptive roles of these SNVs.