Population genomics studies identify signatures of global dispersal and drug resistance in Plasmodium vivax

Abstract

Plasmodium vivax is a major public health burden, responsible for the majority of malaria infections outside Africa. We explored the impact of demographic history and selective pressures on the P. vivax genome by sequencing 182 clinical isolates sampled from 11 countries across the globe, using hybrid selection to overcome human DNA contamination. We confirmed previous reports of high genomic diversity in P. vivax relative to the more virulent Plasmodium falciparum species; regional populations of P. vivax exhibited greater diversity than the global P. falciparum population, indicating a large and/or stable population. Signals of natural selection suggest that P. vivax is evolving in response to antimalarial drugs and is adapting to regional differences in the human host and the mosquito vector. These findings underline the variable epidemiology of this parasite species and highlight the breadth of approaches that may be required to eliminate P. vivax globally.

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

“…As these species have emerged from the bottleneck, they likely have undergone both sustained and recent selection. In the case of P. vivax, previous work has demonstrated that long-term diversifying and directional selection has shaped its genetic diversity (63,68). Our data are consistent with this finding, showing minimal structuring in the P. vivax population but evidence of strong directional selection in multiple regions of the genome.…”

“…However, we cannot rule out the possibility that other selective pressures have also affected parasite population structuring, for example, widespread deforestation and climate change altering the diversity of Anopheline vectors or evolving host-parasite interactions within mosquito vectors. In P. vivax, a strong New World vs. Old World divide correlates with genetic variation in pvs47, the ortholog of pfs47, which has been associated with differential infectivity in different mosquito species (63,64). However, both Anopheles dirus s.s. and Anopheles minimus s.s., the main malaria vectors in Cambodia, are adept at transmitting both P. falciparum and P. vivax (65,66).…”

“…Evidence has shown that both species of malaria are significantly less diverse than primate malarias and likely have undergone genetic bottlenecks associated with host switching and emergence out of Africa, likely less than 10,000 y ago (63,(68)(69)(70)(71)(72). As these species have emerged from the bottleneck, they likely have undergone both sustained and recent selection.…”

Mitochondrial DNA from the eradicated European Plasmodium vivax and P. falciparum from 70-year-old slides from the Ebro Delta in Spain

“…SRP081144). At the nuclear level, the American isolates show geographic differentiation but also a common clustering regarding the Old World populations (5).…”

“…For example, the current global distribution of P. vivax includes Asia, the Middle East, South and Central America, and parts of Africa (3) and has likely resulted from complex dispersals involving intercontinental human population movements (4,5). Although an African origin is likely (6), the current strains from this continent show little genetic polymorphism compared with the rest of the world (4), a fact that has been related to the emergence of Duffy-negative blood types-resistant to P. vivax-in human populations from this continent (7).…”