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. African apes harbour six Plasmodium species, one of which gave rise to the human malaria parasite. Here, Sundaraman et al . use selective whole-genome amplification to determine genome sequences from two chimpanzee Plasmodium species, shedding light on the evolutionary origin of the human parasite.