Genomic_and_transcriptomic_comparisons_of_closely_related_malaria_parasites_differing_in_virulence_and_sequestration_pattern. Genomic_and_transcriptomic_comparisons_of_closely_related_malaria_parasites_differing_in_virulence_and_sequestration_pattern

Malaria parasite species differ greatly in the harm they do to humans. While P. falciparum kills hundreds of thousands per year, P. vivax kills much less often and P. malariae is relatively benign. Strains of the rodent malaria parasite Plasmodium chabaudi show phenotypic variation in virulence during infections of laboratory mice. This makes it an excellent species to study genes which may be responsible for this trait. By understanding the mechanisms which underlie differences in virulence we can learn how parasites adapt to their hosts and how we might prevent disease. Here we present a complete reference genome sequence for the more virulent PcCB strain, and perform a detailed comparison with the genome of the less virulent PcAS strain. We found the greatest genomic variation in the subtelomeric regions, in particular amongst the sequences of the pir gene family, which has been associated with virulence and establishment of chronic infection. However, despite substantial variation at the sequence level, the repertoire of these genes has been largely maintained, highlighting the requirement for functional conservation as well as diversification in host-parasite interactions. We found that core genes involved in red blood cell invasion and sexual development have been under positive selection and these parallel phenotypic differences between parasite strains. These results provide the basis for a mechanistic understanding of the phenotypic differences between Plasmodium chabaudi strains, which might ultimately be translated into a better understanding of malaria parasites affecting humans.