A New Malaria Agent in African Hominids

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Abstract
Plasmodium falciparum is the major human malaria agent responsible for 200 to 300 million infections and one to three million deaths annually, mainly among African infants. The origin and evolution of this pathogen within the human lineage is still unresolved. A single species, P. reichenowi, which infects chimpanzees, is known to be a close sister lineage of P. falciparum. Here we report the discovery of a new Plasmodium species infecting Hominids. This new species has been isolated in two chimpanzees (Pan troglodytes) kept as pets by villagers in Gabon (Africa). Analysis of its complete mitochondrial genome (5529 nucleotides including Cyt b, Cox I and Cox III genes) reveals an older divergence of this lineage from the clade that includes P. falciparum and P. reichenowi (∼21±9 Myrs ago using Bayesian methods and considering that the divergence between P. falciparum and P. reichenowi occurred 4 to 7 million years ago as generally considered in the literature). This time frame would be congruent with the radiation of hominoids, suggesting that this Plasmodium lineage might have been present in early hominoids and that they may both have experienced a simultaneous diversification. Investigation of the nuclear genome of this new species will further the understanding of the genetic adaptations of P. falciparum to humans. The risk of transfer and emergence of this new species in humans must be now seriously considered given that it was found in two chimpanzees living in contact with humans and its close relatedness to the most virulent agent of malaria. In 2002, the publication of the genome of Plasmodium falciparum, the most malignant agent of malaria, generated hopes in the fight against this deadly disease by the opportunities it offered to discover new drug targets. Since then results have not lived up to the expectations. The development of comparative genomics to further understanding of P. falciparum has indeed been hindered by a lack of knowledge of closely related species' genomes. Only one species, P. reichenowi, infecting chimpanzees, was hitherto known as a sister lineage of P. falciparum. Here we describe a new Plasmodium species infecting chimpanzees in Africa. Based on its whole mitochondrial genome, we demonstrate that this species is a relative of P. falciparum and P. reichenowi. The analysis of its genome should thus offer the opportunity to explore P. falciparum specific adaptations to humans. Our results bring new elements to the debate surrounding the origin of this lineage. They suggest that it may have been present in early hominoids and may have experienced a radiation congruent with that of its hosts. Our discovery highlights the paucity of our knowledge on the richness of Plasmodium species infecting primates and calls for more research in this direction.