Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria

Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite P. praefalciparum. Little is known about the other gorilla and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers as well as convergent evolution were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor shows a host specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate confidently for the first time the timing of the beginning of speciation to be 40,000-60,000 years ago followed by a population bottleneck around 4,000-6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans.