Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution

Abstract

Plasmodium vivax is responsible of the majority of malaria infections outside Africa. Its closer genetic relative, Plasmodium vivax--like, was discovered in African great apes and suggested to have given rise to P. vivax in humans. We generated two newly P.vivax--like reference genomes and 9 additional P. vivax--like genotypes, to unravel the evolutionary history of P. vivax. We showed a clear separation between the two clades, a higher genetic diversity of P. vivax--like parasites in comparison to the P. vivax ones, and the potential existence of two sub--clades of P. vivax--like. We dated the relative split between P. vivax and P. vivax--like as three times shorter than the split between P. ovale wallikeri and P. ovale curtesi and 1.5 times longer than the split between Plasmodium malariae. The sequencing of the P. vivax--like genomes is an undeniable advance in the understanding of P. vivax biology, evolution and emergence in human populations. not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. Significance statementsThe copyright holder for this preprint (which was . http://dx.doi.org/10.1101/205302 doi: bioRxiv preprint first posted online 3 Main text.Plasmodium vivax, the most prevalent human malaria parasite outside Africa, is responsible for severe and incapacitating clinical symptoms in humans 1 . Traditionally, P. vivax has been neglected because of its lower mortality in comparison to Plasmodium falciparum 2,3 . Its ability to produce a dormant liver--stage form (hypnozoite), responsible of relapsing infections, makes it a challenging public health issue for malaria elimination.The recent emergence of antimalarial drug resistance 4 as well as the discovery of severe and even fatal human cases 2,5,6 has renewed the interest for this enigmatic species, including its evolutionary history and its origin in humans.Earlier studies placed the origin of P. vivax in humans in Southeast Asia ("Out of Asia" hypothesis) based on its phylogenetic position in a clade of parasites infecting Asian monkeys 7 . At that time, the closest known relative of P. vivax was considered to be Plasmodium cynomolgi, an Asian monkey parasite 8 . However, this hypothesis was recently challenged with the discovery of another Plasmodium species, genetically closer to P. vivax than P. cynomolgi, circulating in African great apes (chimpanzees and gorillas) 9,10 . This new lineage (hereafter named Plasmodium vivax--like) was considered by certain authors to have given rise to P. vivax in humans following a transfer of parasites from African apes 10 , but this "Out of Africa" hypothesis still remains debated.Moreover, a transfer of P. vivax--like parasites has been documented, thus making possible the release of new strains in new hosts species, specifically in human populations 9 . In such a context, it now seems fundamental to characterize the genome of the closest ape--relative to the human P. vivax parasite in order to get a better understanding of the evolution of this para...

Investigating the Characteristics and Evolution of Apical Membrane Antigen 1 (AMA1) of Plasmodium sp. using Phylogenetic Approach in Searching for Drug Candidate

“…In details, P. coatneyi infection could induce severe anemia, coagulopathy, renal impairment, and metabolic dysfunction, similar to human cases of malaria [25]. An interesting study revealed that the genomes of P. knowlesi, P. vivax, P. coatneyi and P. cynomolgi were hypothesized coming from the similar ancestor and create the monkey clade in plasmodium phylogenetic tree [12], in accordance to our reported result in AMA-1 phylogenetic tree. The elucidation of the P. cynomolgi and P.…”

“…This indicates the evolutionary hypothesis is similar within those algorithms. Several studies also reported the same topology as our tree although the molecular marker is different [12], [13]. The tight grouping, in terms of branch length, within the same species suggested that AMA-1 is conserved to a certain degree intraspecies.…”

“…coatneyi genomic sequences could serve a critical step in creating a model system to treat P. vivax, one of the major malaria agent outside Africa [12], [14]. It could also be true for AMA-1 protein vaccine design.…”

“…The polymorphic feature of AMA-1 leads to a challenge in the process of vaccine design [8], [11]. The evolutionary relationship of the plasmodium species has been reported using several molecular markers [12]-- [14], but the AMA-1 evolutionary relationship among the plasmodium species is not yet elucidated.…”

Origin of Two Most Virulent Agents of Human Malaria:Plasmodium falciparumandPlasmodium vivax

“…Today, an interesting question would be to understand how this passage of apes to man had been done. To this question, in view of current data and analyses, we agree to say, instead, it is much more likely that extant human P. vivax could represent a lineage that survived after spreading out of Africa [21,64,65], because this theory could explain the fact that we observed today a reduced diversity of the human parasites which would result from an out-of-Africa bottleneck, such as observed in P. falciparum [45,66].…”