Rodent malaria parasites : genome organization & comparative genomics

Abstract

The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P. falciparum and partial genome sequences of three RMPs (Plasmodium yoelii - Chapter 3; Plasmodium berghei and Plasmodium chabaudi - Chapter 4) enabled us to expand the analysis to a genome-wide survey. By aligning the RMP contigs against the P. falciparum genome, a composite RMP genome was constructed, which was subsequently compared in detail with the P. falciparum genome (Chapter 5). These comparative analyses showed high levels of conservation in both genome organization and gene content (~85%), supporting the use of RMPs as models for human malaria infection. P. falciparum-specific genes located in both subtelomeric and core regions of the chromosomes were also found and included many genes involved in host-parasite interactions, such as host cell invasion and evasion of the human immune response. Finally, reverse genetics approaches were used to study the function of certain genes that are conserved between the rodent and human malaria parasites (Chapters 6 & 7).