Ape parasite origins of human malaria virulence genes

Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum

Genomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria

African apes harbour at least six Plasmodium species of the subgenus Laverania, one of which gave rise to human Plasmodium falciparum. Here we use a selective amplification strategy to sequence the genome of chimpanzee parasites classified as Plasmodium reichenowi and Plasmodium gaboni based on the subgenomic fragments. Genome-wide analyses show that these parasites indeed represent distinct species, with no evidence of cross-species mating. Both P. reichenowi and P. gaboni are 10-fold more diverse than P. falciparum, indicating a very recent origin of the human parasite. We also find a remarkable Laverania-specific expansion of a multigene family involved in erythrocyte remodelling, and show that a short region on chromosome 4, which encodes two essential invasion genes, was horizontally transferred into a recent P. falciparum ancestor. Our results validate the selective amplification strategy for characterizing cryptic pathogen species, and reveal evolutionary events that likely predisposed the precursor of P. falciparum to colonize humans

The use of molecular methods in studies of avian haemosporidians

During the last two decades, molecular methods to study mitochondrial DNA sequence variation have become an important part in the studies of avian haemosporidians. Up until recently, these methods have primarily been used for identification of the parasites and for tentative phylogenetic reconstructions, allowing researchers not trained in traditional parasitology to compare data across the globe. However, with the introduction of genome and transcriptome sequencing, studies are emerging that go deeper into the genetics and molecular biology of the parasites. In this chapter, we describe and summarize the common methods used for genetic barcoding of the parasites and give an introduction of what to take into account when designing a molecular study of avian haemosporidians. This chapter further discusses why nuclear genetic data are needed in order to answer several important ecological and evolutionary questions and which methods to use in order to overcome the obstacles of obtaining nuclear data of the parasites. Finally, this chapter highlights the challenges and opportunities that come with the use of molecular methods, such as how to study and interpret prevalence, the challenge of aborted developments, and how to obtain data for more robust phylogenies and population structure studies of the parasites