Origin of the human malaria parasite Plasmodium falciparum in gorillas

Abstract

Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.

Figure 1. Location of ape study sites

Field sites are shown in relation to the ranges of three subspecies of the common chimpanzee (P. t. ellioti, magenta; P. t. troglodytes, red; and P. t. schweinfurthii, blue), western (Gorilla gorilla, red stripes) and eastern (Gorilla beringei, black stripes) gorillas, and the bonobo (Pan paniscus, orange) in sub-Saharan Africa. Forested areas are indicated in green, while arid areas are shown in yellow (map courtesy of Lilian Pintea, The Jane Goodall Institute). Circles, squares and hexagons identify field sites where chimpanzees, gorillas, or both species were sampled, respectively (ovals indicate bonobo collection sites). Sites where ape malaria was detected are highlighted in yellow, with red lettering indicating that both chimpanzees and gorillas were infected.

Figure 2. Phylogeny of Plasmodium parasites from wild-living chimpanzees and western gorillas

A representative subset of 146 SGA-derived Plasmodium mitochondrial cytochrome B sequences (956 bp) is shown in relation to human and simian Plasmodium reference sequences (for accession numbers see Supplementary Tables 6 and 7). The full set of 697 SGA-derived ape Plasmodium sequences is analyzed in Supplementary Fig. 3. Sequences are color-coded, with capital letters indicating the field site (Fig. 1) and lower case letters denoting species and subspecies origin (ptt: P. t. troglodytes, red; pte: P. t. ellioti, orange; pts: P. t. schweinfurthii, blue; gor: G. g. gorilla, green). C1-C3 and G1-G3 represent chimpanzee and gorilla specific Plasmodium species, respectively, all of which are included within the subgenus Laverania. The tree was inferred using maximum likelihood methods. Bootstrap values (above 70%) are indicated for major nodes only (the scale bar represents 0.01 substitutions per site).

Figure 3. Evolutionary relationships of ape and human Plasmodium parasites in mitochondrial coding and non-coding regions

a,b, Phylogenetic trees of SGA-derived mitochondrial (a) CytB, CoxI and CoxIII protein (980 amino acids) and (b) non-overlapping nucleotide sequences (2,501 bp) of the closest chimpanzee (C1) and gorilla (G1) relatives of human P. falciparum (see Supplementary Fig. 1a for the position of the corresponding 3.4 kb and 3.3 kb SGA amplicons). Plasmodium sequences are labeled and color-coded as in Fig. 2, except for sequences derived from captive bonobos (Bo), which are shown in magenta. Human P. falciparum (Hu) and chimpanzee reference sequences are depicted in black, with the number of human sequences representing the same haplotype shown in parentheses (for accession numbers see Supplementary Table 7). The trees were inferred using maximum likelihood methods; numbers at nodes indicate bootstrap (above) and posterior probability (below) values, respectively (only values above 70 and 0.7 are shown). The scale bars represent 1 amino acid (aa) and one nucleotide (nt) substitution per site, respectively.