The Diversity Landscape of Plasmodium falciparum var Genes

Githinji, George Lloyd (2016). The Diversity Landscape of Plasmodium falciparum var Genes. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000ef9d

Abstract

Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) is an important group of cytoadhesive multi-domain Plasmodium falciparum surface antigens that are inserted onto the surface of infected erythrocytes and are encoded by the var multi-gene family. PfEMP1 antigens are thought to be important targets of naturally acquired immunity to malaria. This thesis describes nucleotide variation in DBLα sequence tags, a semi-conserved region within the DBLα domain that can be PCR amplified using universal primers. PfEMP1 can be classified using a number of approaches some of which are associated with particular expression patterns in severe, non-severe and asymptomatic malaria. This work compared the classification approaches with an aim of understanding the extent of overlap or discordance between them. To explore non-random distribution of variation in respect to var’s functional specialization, a clustering approach was developed and applied in exploring patterns of nucleotide variation among var subsets from different geographical locations in addition to distribution of predicted B and T-cell epitopes among the var subsets. In summary the sequences showed distinct patterns of nucleotide substitution that suggests that var sequences are under both diversifying and purifying selection.