A monkey's tale: The origin of Plasmodium vivax as a human malaria parasite

Abstract

The high prevalence of Duffy negativity (lack of the Duffy blood group antigen) among human populations in sub-Saharan Africa has been used to argue that Plasmodium vivax originated on that continent. Here, we investigate the phylogenetic relationships among 10 species of Plasmodium that infect primates by using three genes, two nuclear (␤-tubulin and cell division cycle 2) and a gene from the plastid genome (the elongation factor Tu). We find compelling evidence that P. vivax is derived from a species that inhabited macaques in Southeast Asia. Specifically, those phylogenies that include P. vivax as an ancient lineage from which all of the macaque parasites could originate are significantly less likely to explain the data. We estimate the time to the most recent common ancestor at four neutral gene loci from Asian and South American isolates (a minimum sample of seven isolates per locus). Our analysis estimates that the extant populations of P. vivax originated between 45,680 and 81,607 years ago. The phylogeny and the estimated time frame for the origination of current P. vivax populations are consistent with an ''out of Asia'' origin for P. vivax as hominoid parasite. The current debate regarding how the Duffy negative trait became fixed in Africa needs to be revisited, taking into account not only human genetic data but also the genetic diversity observed in the extant P. vivax populations and the phylogeny of the genus Plasmodium.Duffy ͉ genetic diversity ͉ host-switch

The genetic diversity of Plasmodium vivax: a review

“…This argument was also supported by the abundance of simian malaria parasite species in Asia and the presence of several macaque parasites that shared similar morphological and biological characteristics with P. vivax (Carter 2003). This hypothesis has been well accepted in recent years (Escalante et al 2005, Jongwutiwes et al 2005.…”

“…In this investigation, most of the data was not compatible with the explanation that P. vivax was a Homo parasite before the expansion of the hominoid populations out of Africa. Hence, the authors suggest that P. vivax was probably derived from ancestral macaque parasites when hominoids colonized Southeast Asia (Escalante et al 2005).…”

“…A previous study suggested that P. falciparum is older than P. vivax (Escalante et al 1995), and the virulence of P. falciparum has been attributed to the fact that it recently became a human parasite due to a host switch (probably, birds) between 5,000 to 10,000 years ago (Boyd 1949, Livingstone 1958, Snewin et al 1991, Escalante et al 1995. Low microsatellite and tandem repeat variability may indicate that P. vivax has only infected humans recently (10,000 years ago) (Leclerc et al 2004), however a different study based on polymorphisms of two nuclear and one plastid gene places the origin at between 45,000 and 81,000 years ago (Escalante et al 2005). Through these preliminary studies, two major conclusions were reached: (a) malaria parasites arose independently as human pathogens and, (b) P. reichenowi, a chimpanzee parasite, is the species that shares the most recent common ancestor with P. falciparum (Escalante et al 1995).…”

“…Nevertheless, for that to have really happened, the presence of a strong selection factor would have be necessary, which seems unlikely as P. vivax does not exhibit high levels of virulence in terms of mortality rates. For this reason, it is probable that the Duffy-negative genotype present on the African continent, could have been fixed by another process (selection due to another pathogen or chance) and then became a barrier against the introduction of P. vivax (Carter 2003, Escalante et al 2005. Also attempts to test this hypothesis starting from an investigation of two nuclear genes, b-tubulin and cell division cycle 2 and a gene from the plastid genome, the elongation factor Tu (TufA) were made.…”

“…It seems very probable that Duffy-negative homozygote individuals (lack of the Duffy blood group antigen), are completely protected against P. vivax infection (Escalante et al 2005). Thus, the high prevalence of these genotypes among African populations, has been used to supplant P. vivax origin on this continent, showing that a selective pressure might have been generated in favor of the survival of the parasite organism, because the presence of the Duffy protein is essential for the merozoite invasion of red blood cells.…”