Ancient Introgression between Two Ape Malaria Parasite Species

Abstract

The Laverania clade comprises the human malaria parasite Plasmodium falciparum as well as at least seven additional parasite species that infect wild African apes. A recent analysis of Laverania genome sequences (Otto TD, et al. 2018. Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria. Nat Microbiol. 3: 687-697) reported three instances of interspecies gene transfer, one of which had previously been described. Generating gene sequences from additional ape parasites and re-examining sequencing reads generated in the Otto et al. study, we identified one of the newly described gene transfers as an assembly artifact of sequences derived from a sample coinfected by two parasite species. The second gene transfer between ancestors of two divergent chimpanzee parasite lineages was confirmed, but involved a much larger number of genes than originally described, many of which encode exported proteins that remodel, or bind to, erythrocytes. Because successful hybridization between Laverania species is very rare, it will be important to determine to what extent these gene transfers have shaped their host interactions.

Keywords: Laverania; Plasmodium; chimpanzee; exported proteins.

Fig. 1.

—Relationships among Laverania species. (a) The standard topology for the eight known Laverania species (Liu et al. 2010, 2016, 2017). Colors indicate the parasite’s usual host species: Bonobos (purple), chimpanzees (blue), humans (black), and gorillas (red). Although most prevalent in chimpanzees, P. gaboni (and on rare occasions P. reichenowi) also infects bonobos (Liu et al. 2017). The tree was derived by maximum likelihood analysis of a 3.4 kb region of the mitochondrial genome (see Supplementary Fig. 1a in Liu et al. 2010). (b) Schematic representation of an anomalous topology with transfer from P. gaboni to P. billcollinsi (termed “topology C” in Supplementary Figure 5 of Otto et al. 2018). (c) Schematic representation of an anomalous topology with transfer between P. reichenowi and P. billcollinsi (termed “topology D” in Supplementary Figure 5 of Otto et al. 2018). (d) Maximum likelihood tree of one of four genes (gene ID PF3D7_1328000) hypothesized to have resulted from P. gaboni to P. billcollinsi gene transfer (Otto et al. 2018). Sequences were obtained from published reference genomes (black), limiting dilution PCR from ape blood or fecal samples collected at three field sites (SY, GT, TL), or de novo assembled contigs of sequencing data released by Otto et al. (labelled with the name of the animal from which the data were derived: Toudy, Nzigou, Cerise, Lolita; see Supplementary Table 1 of Otto et al. 2018). For PCR-derived sequences and new contigs, color indicates whether the sample was obtained from a chimpanzee (blue) or a bonobo (purple). Note that the sequence from the published P. billcollinsi reference genome clusters within P. gaboni, whereas other P. billcollinsi sequences fall in the expected position within the tree. The scale bar represents 0.005 nucleotide substitutions per site; bootstrap values from 100 replicates are shown for interspecific branches with at least 70% support.

Fig. 2.

—Chromosomal regions revealing an ancient introgression event. (a, b) Regions on chromosomes 1 and 9, respectively. On the chromosome bar, regions with the standard topology are shown in white, regions with the anomalous topology in red; gray indicates topology is unclear. Above this, the positions of exons are shown for genes (solid gray) and pseudogenes (hatched), along with the name of the putative gene product. Bars above the genes indicate regions for which trees were generated, in black (PCR amplicons, newly assembled contigs, and published data) or gray (newly assembled contigs and published data only); four of these are shown in the upper panels, whereas additional trees are shown in supplementary Material online. Coloring and labeling of trees are as for fig. 1d. Scale bars represent 0.02 nucleotide substitutions per site; bootstrap values from 100 replicates are shown for interspecies nodes with at least 70% support; trees are rooted between the P. gaboni plus P. adleri clade and the other species. Exported, Plasmodium exported protein, unknown function; LPL, lysophospholipase; probable, probable protein, unknown function. On chromosome 9, phistb is absent from both the P. reichenowi and P. billcollinsi genome assemblies.