The Evolutionary History of Plasmodium vivax as Inferred from Mitochondrial Genomes: Parasite Genetic Diversity in the Americas

Abstract

Plasmodium vivax is the most prevalent human malaria parasite in the Americas. Previous studies have contrasted the genetic diversity of parasite populations in the Americas with those in Asia and Oceania, concluding that New World populations exhibit low genetic diversity consistent with a recent introduction. Here we used an expanded sample of complete mitochondrial genome sequences to investigate the diversity of P. vivax in the Americas as well as in other continental populations. We show that the diversity of P. vivax in the Americas is comparable to that in Asia and Oceania, and we identify several divergent clades circulating in South America that may have resulted from independent introductions. In particular, we show that several haplotypes sampled in Venezuela and northeastern Brazil belong to a clade that diverged from the other P. vivax lineages at least 30,000 years ago, albeit not necessarily in the Americas. We propose that, unlike in Asia where human migration increases local genetic diversity, the combined effects of the geographical structure and the low incidence of vivax malaria in the Americas has resulted in patterns of low local but high regional genetic diversity. This could explain previous views that P. vivax in the Americas has low genetic diversity because these were based on studies carried out in limited areas. Further elucidation of the complex geographical pattern of P. vivax variation will be important both for diversity assessments of genes encoding candidate vaccine antigens and in the formulation of control and surveillance measures aimed at malaria elimination.

Using Mitochondrial Genome Sequences to Track the Origin of Imported Plasmodium vivax Infections Diagnosed in the United States

“…[34][35][36] A very recent analysis of mitochondrial lineages of P. vivax sampled across the Americas confirmed the high level of genetic diversity and substructuring of local parasite populations, with at least four well-defined haplotype clusters. 37 These data are consistent with the introduction of P. vivax in the Americas from multiple sources and at different times since the first humans reached the continent in preColumbian times. This hypothetical scenario may explain why some mitochondrial lineages of American parasites cluster together with the lineages from Africa and south Asia and a few lineages are connected to Melanesian lineages, whereas most lineages have clearly diverged from all other P. vivax populations (Figures 1 and 2).…”

Uncovering the transmission dynamics ofPlasmodium vivaxusing population genetics

“…Previous analyses suggested an Asian origin based on high mtDNA diversity in this region, but are likely to have been influenced by the lack of African parasites in the sample and by demographic processes such as population expansion, which increases diversity. 44 There have been some attempts to understand how P. vivax subsequently spread around the world using mtDNA [34][35][36]45 ; however, the population structure is complex and requires further deep sampling of strains from all major endemic regions. Nevertheless, some important insights have been gained into the evolutionary history of P. vivax in different geographic regions.…”

“…Nevertheless, some important insights have been gained into the evolutionary history of P. vivax in different geographic regions. For example, in South America, there is low local diversity but high divergence consistent with multiple independent introductions 35 possibly from a European source with origins in Africa. 45 Whereas in the Asia Pacific, high local diversity is observed, consistent with ancient population expansion and complex migration patterns.…”

“…45 Whereas in the Asia Pacific, high local diversity is observed, consistent with ancient population expansion and complex migration patterns. 35,36,46 The reanalysis of new sequences from key geographic areas together with the available dataset of mtDNA sequences (currently more than 700 sequences) will undoubtedly shed further light on the complex past of P. vivax. Interestingly, while P. falciparum diversity is tightly associated with regional levels of endemicity, P. vivax harbours high genetic diversity across all endemicities (Fig.…”

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

“…Alternatively, it has been suggested that modern African parasites, at least in the Horn of Africa and Madagascar, could have been reintroduced via the import of East Asian/Indian P. vivax to the coastal areas of East Africa by early seagoing traders and that this could explain their lack of diversity (4). Intriguingly, the diversity of the American strains is comparable to those found in Oceania and Asia (8), raising questions regarding the origin of these strains. Some of the American strains are thought to have been brought there from Europe by Spanish sailors and colonists in the last few centuries (4,9).…”