Malarial parasite diversity in chimpanzees: the value of comparative approaches to ascertain the evolution of Plasmodium falciparum antigens

Abstract

BackgroundPlasmodium falciparum shares its most recent common ancestor with parasites found in African apes; these species constitute the so-called Laverania clade. In this investigation, the evolutionary history of Plasmodium lineages found in chimpanzees (Pan troglodytes) was explored.MethodsHere, the remainders of 74 blood samples collected as part of the chimpanzees’ routine health examinations were studied. For all positive samples with parasite lineages belonging to the Laverania clade, the complete mitochondrial genome (mtDNA), the gene encoding dihydrofolate reductase-thymidylate synthase (dhfr-ts), the chloroquine resistance transporter (Pfcrt), the circumsporozoite protein (csp), merozoite surface protein 2 (msp2), and the DBL-1 domain from var2CSA were amplified, cloned, and sequenced. Other Plasmodium species were included in the mtDNA, dhfr-ts, and csp analyses. Phylogenetic and evolutionary genetic analyses were performed, including molecular clock analyses on the mtDNA.Results/ConclusionsNine chimpanzees were malaria positive (12.2%); four of those infections were identified as P. falciparum, two as a Plasmodium reichenowi-like parasite or Plasmodium sp., one as Plasmodium gaboni, and two as Plasmodium malariae. All P. falciparum isolates were resistant to chloroquine indicating that the chimpanzees acquired such infections from humans in recent times. Such findings, however, are not sufficient for implicating chimpanzees as an animal reservoir for P. falciparum.Timing estimates support that the Laverania clade has co-existed with hominids for a long-period of time. The proposed species P. gaboni, Plasmodium billbrayi, and Plasmodium billcollinsi are monophyletic groups supporting that they are indeed different species.An expanded CSP phylogeny is presented, including all the Laverania species and other malarial parasites. Contrasting with other Plasmodium, the Laverania csp exhibits great conservation at the central tandem repeat region. Msp2 and var2CSA, however, show extended recent polymorphism in P. falciparum that likely originated after the P. reichenowi-P. falciparum split. The accumulation of such diversity may indicate adaptation to the human host. These examples support the notion that comparative approaches among P. falciparum and its related species will be of great value in understanding the evolution of proteins that are important in parasite invasion of the human red blood cell, as well as those involved in malaria pathogenesis.

Ape malaria transmission and potential for ape-to-human transfers in Africa

“…Several authors have speculated about the possibility that apes could be a source of new Plasmodium infections for humans and vice versa, providing a mosquito species could act as bridge between these different host species (5,17). Several recent studies have indeed reported transfers of Plasmodium from apes to humans or humans to apes in certain conditions, but the mosquitoes involved in these transfers were never identified (4,7,9,33).…”

“…Our results demonstrated that all ape parasites are transmitted by the same three vector species, thus rejecting the hypothesis that vectors could be responsible for the Laverania host specificity. sanctuary (9), suggesting that host switches are possible under certain conditions, and hence that the species barrier might be porous. Therefore, other factors could contribute to this strong host/parasite association observed in natura in the Laveranias.…”

Wild African great apes as natural hosts of malaria parasites: current knowledge and research perspectives

“…Analysis of var and var-like gene sequences from human and ape Laverania species showed that many characteristics of these genes are conserved across the different Laverania species and that these evolved well before the emergence of all the Laverania species (Larremore et al, 2015). In addition, the var2csa genes, known to be associated with the adherence of P. falciparum-infected erythrocytes to the placenta and placental malaria in humans, have also been identified in P. reichenowi and P. gaboni (Pacheco et al, 2013;Trimnell et al, 2006). However, the question of whether the expression of var genes is also associated with pathogenicity in AGAs remains open.…”

Anthropogenics: Human Influence on Global and Genetic Homogenization of Parasite Populations

“…The absence of such ''silent'' variation indicated that these far-flung isolates shared very recent common ancestry. It further demonstrated that subsequent differentiation among regional populations was minimal, and restricted to sites undergoing exceptionally rapid differentiation, i.e., microsatellite repeats, or to sites experiencing strong selective pressure, i.e., drug resistance and immune evasion alleles Ayala, 1998, 2000;Mita et al, 2009aMita et al, , 2009bVinayak et al, 2010;Mita and Tanabe, 2012;Mallick et al, 2013;Pacheco et al, 2013). These findings illustrate the need for a proper context in interpreting patterns of genetic variability or, in this case, what seemed a notable lack of variability.…”

“…Answering these questions required identifying useful population comparisons (Pacheco et al, 2013). Phylogenetic inferences as to the ultimate origins of P. falciparum required improved sampling.…”