| Summary: | Developmentally-linked gene expression is critical to the success of the human malaria parasite Plasmodium alciparum in ensuring colonisation, adaptation, replication and transmission during its complex life cycle as well as the manifestation of disease in humans. Yet, despite the wealth of high-throughput transcriptomic data, our understanding of the organisation of the transcriptional unit outside of the open reading frame is limited. The objectives of this study were directed towards understanding how intergenic space is organised over the entire P. falciparum genome and determining the likely spatio-temporal organisation of transcripts over these intergenic regions. In addition, as homopolymeric poly dA.dT are significantly overrepresented within these regions, a spatial analysis of poly dA.dT tract positional bias was undertaken and correlated with available nucleosome positioning data. These studies in P. falciparum were supported with comparative analyses using a range of other Apicomplexan parasites. Finally, the role of the 5’ untranslated region in directing transcriptional and translational efficiency for a typical housekeeping gene was investigated. Towards these aims a range of approaches were employed including bioinformatics, comparative genomics, data modelling and reporter gene assays. The findings presented in this thesis extend our understanding of the transcriptional landscape in this important human pathogen, generating models that can be experimentally validated when new RNAseq datasets become available. Ideas relating to how different selective forces are at play in shaping the organisation and sequence of intergenic regions are also presented. Moreover, we demonstrate comparable organisations of intergenic regions and homopolymer tracts within a number of Apicomplexan parasites, many important for human and animal health, providing the basis for a comparative approach to understanding transcriptional processes across this medically important phylum.
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