Malaria imposes a huge burden on human health. We are studying the genetic diversity of malaria parasites in order to elucidate their history and adaptive evolution mechanisms.
(1) Population genetics of malaria parasites
The human malaria parasite Plasmodium falciparum infects only humans. Consequently, the evolution of this parasite is presumed to be intimately associated with humans. To examine this association, we are investigating the genetic diversity of P. falciparum populations from diverse geographic areas. We have observed a clear negative correlation between the within-population genetic diversity and the geographic distance from East Africa to Asia and Oceania, which mirrors the isolation-by-distance of modern humans. Age estimates support the notion that modern humans carried the parasite along during their colonization of the world.
Fig. 1. Negative correlation between the within-population genetic diversity of P. falciparum and the geographic distance from East Africa to Asia and Oceania. This suggests that the parasite spread together with modern humans during their out-of-Africa colonization.
(2) The evolution of antigenic polymorphism in malaria parasites
One way malaria parasites evade the host”Ēs immune system is through antigenic polymorphism. We are investigating human parasite populations from diverse geographic areas, as well as monkey malaria parasites, to reveal the evolutionary origins and population genetic mechanisms that drive antigenic polymorphism in immune-target genes.
(3) Co-evolution between malaria parasites and their hosts
While malaria parasites infect all classes of terrestrial vertebrates (mammals, birds, and reptiles), each parasite species infects only one specific host. Such wide host range and high host specificity indicate that malaria parasites have a close relationship with their hosts. To examine this parasite-host co-evolution, we compared the evolutionary histories of malaria parasites and their hosts. We found that all of the extant lineages of malaria parasites originated during a period of rapid diversification that involved host switches.
Fig. 2. Malaria big bang in the evolution of extant malaria parasites. The diversification (beige bar) occurred much later than the emergence of host animals, which suggests that host switching led to the diversification of the parasite lineage.
(4) Genome sequencing of a P. vivax-related monkey malaria parasite, P. cynomolgi
The human malaria parasite P. vivax became a parasite of humans by host switching from a monkey. To clarify the genetic changes that are specific to P. vivax, we are genome sequencing a P. vivax-related monkey malaria parasite, P. cynomolgi. The sequencing is currently at the gap closure and annotation step, and a draft genome will be complete soon. Comparative genomics has already revealed gene gains/losses that are specific to P. vivax.
Fig. 3. Genome sequencing of P. cynomolgi, a monkey malaria parasite that is closely related to P. vivax, by using the new sequencing system (in collaboration with Dr. S. Kawai at Dokkyo Med. Univ.).