The origin and age of Plasmodium vivax

Abstract

The evolutionary history of Plasmodium vivax has recently been addressed in terms of its origin as a parasite of humans and the age of extant populations. The consensus is that P. vivax originated as a result of a host switch from a non-human primate to hominids and that the extant populations did not originate as recently as previously proposed. Here, we show that, in a comparison of parasite isolates from across the world, Asian populations of P. vivax are the oldest. We discuss how this result, together with the phylogenetic evidence that P. vivax derived from Plasmodium found in Southeast Asian macaques, is most simply explained by assuming an Asian origin of this parasite. Nevertheless, the available data show only the tip of the iceberg. We discuss how sampling might affect time estimates to the most recent common ancestor for P. vivax populations and suggest that spatially explicit estimates are needed to understand the demographic history of this parasite better.

Figure 1

Bayesian phylogenetic tree using complete mitochondrial genomes for parasites of Southeast Asian primates and Plasmodium simium, using Plasmodium gonderi as the outgroup. This phylogenetic tree was inferred under the Hasegawa–Kishino–Yano (HKY) substitution model with MrBayes [28]. The search was performed with 1 000 000 generations, and the first 10 000 trees were discarded in the burning (see Ref. [28] for details). Values above branches are posterior probabilities expressed as percentages. A neighbor-joining tree [29] inferred under the Tamura and Nei substitution model with the software MEGA [30] was used as a prior (see Ref. [31] for information about DNA substitution models). P. simium is identical to Plasmodium vivax, indicating a transfer from humans to South American monkeys (see discussion in Refs [10,11]). The tree indicates that P. vivax is closely related to Plasmodium cynomolgi. The P. vivax–P. cynomolgi group diverged from other species of Plasmodium found in non-human primates. This phylogeny indicates that P. vivax originated from a Plasmodium species related to those currently found in Southeast Asian macaques. Branch length is representative of number of nucleotide substitutions per site, as indicated by the scale bar.

Figure 2

Haplotype network showing the relationships among Plasmodium vivax populations. Haplotype network of the 282 mitochondrial genomes (joint datasets) inferred under a median-joining algorithm with posterior pruning using maximum parsimony criteria as implemented in Network 4.1.1.2 [32]. The size of the circles is proportional to the haplotype frequency, with each color indicating the geographic origin of the sample. The Asian populations (dark green) include isolates from China, Thailand, Indonesia and Vietnam. There are 45 haplotypes in 114 sequences from this region, with a haplotype diversity of 0.948. The Melanesian sample (red) includes 32 haplotypes from 73 sequences, with a haplotype diversity of 0.889; the isolates are from Papua New Guinea, Salomon Islands and Vanuatu. The India–Middle-East sample (yellow) includes 16 haplotypes out of 35 sequenced and a haplotype diversity of 0.881. There is more haplotype diversity in Asia and Melanesia than in any other region considered in this analysis. The population from the Americas (blue) has a small number of haplotypes (seven out of 47 sequences and a haplotype diversity of 0.645), smaller, even, than the African population (light green) (eight haplotypes in 12 sequences, with a haplotype diversity of 0.894).