Evolutionary dynamics of zoonotic malaria

点击翻译按钮获取中文摘要

Dozens of malaria species, of the genus Plasmodium, infect human and nonhuman primates worldwide. At least eight of these parasite species have moved from primate reservoirs into human populations, including historical host expansion of P. vivax and P. falciparum, the two primary malaria-causing agents in humans worldwide. As we make progress towards elimination of these common malaria parasites, emerging host switches or expansions that introduce new or rare malaria parasites into human population are an increasing barrier to global elimination. Indeed, in parts of Southeast Asia, a zoonotic malaria parasite is now the main cause of clinical malaria. The lack of genomic resources for zoonotic malaria strains, particularly from wild primates, has been a major barrier to understanding the emergence of malaria parasites and their risk for spread in human populations. Using the emerging zoonotic parasite from Brazil, P. simium, as a case study, we combine whole-genome sequencing of multiple parasite and their host populations to characterize the genetic basis of host specificity and evolution in malaria parasites. P. simium is an ideal system because it is a close relative of the well-studied P. vivax, and importantly, has recently shifted host ranges twice, first from historical human P. vivax into primates, and more recently back into humans. To interpret this new genomic data, we will combine experimental techniques with development of a whole-genome simulation framework that incorporated aspects of parasite lifecycle to better interpret neutral genetic diversity. This opens up recent developments in simulation-based inference techniques that we will use to infer the population history of South American malaria parasites, the timing of zoonoses, and identify loci under selection in multiple hosts. The function of candidate loci identified from computational approaches will then be tested with a specially- developed transgenic line expressing P. simium genes and computational modeling of protein structures from host and parasites. In sum, we combine insights from parasite genomics with complementary analyses of whole genomes from their wild primate hosts—from computational methods development to functional experiments—giving insight into the selective pressures that parasites face inside hosts and host-specific susceptibility.