The Genome of Plasmodium gonderi: Insights into the Evolution of Human Malaria Parasites

Abstract

Plasmodium species causing malaria in humans are not monophyletic, sharing common ancestors with nonhuman primate parasites. Plasmodium gonderi is one of the few known Plasmodium species infecting African old-world monkeys that are not found in apes. This study reports a de novo assembled P. gonderi genome with complete chromosomes. The P. gonderi genome shares codon usage, syntenic blocks, and other characteristics with the human parasites Plasmodium ovale s.l. and Plasmodium malariae, also of African origin, and the human parasite Plasmodium vivax and species found in nonhuman primates from Southeast Asia. Using phylogenetically aware methods, newly identified syntenic blocks were found enriched with conserved metabolic genes. Regions outside those blocks harbored genes encoding proteins involved in the vertebrate host-Plasmodium relationship undergoing faster evolution. Such genome architecture may have facilitated colonizing vertebrate hosts. Phylogenomic analyses estimated the common ancestor between P. vivax and an African ape parasite P. vivax-like, within the Asian nonhuman primates parasites clade. Time estimates incorporating P. gonderi placed the P. vivax and P. vivax-like common ancestor in the late Pleistocene, a time of active migration of hominids between Africa and Asia. Thus, phylogenomic and time-tree analyses are consistent with an Asian origin for P. vivax and an introduction of P. vivax-like into Africa. Unlike other studies, time estimates for the clade with Plasmodium falciparum, the most lethal human malaria parasite, coincide with their host species radiation, African hominids. Overall, the newly assembled genome presented here has the quality to support comparative genomic investigations in Plasmodium.

Keywords: Plasmodium falciparum; Plasmodium vivax; GC content; molecular clock; phylogenomics; synteny.

Fig. 1.

Network plotting the pir gene proteins similarity between P. gonderi (1160 pir), P. cynomolgi M (1048 pir), P. coatneyi Hackeri (496 kir), P. knowlesi H (445 kir), P. vivax-like Pvl01 (311 vir), and P. vivax P01 (1249 vir). The size of each node is determined by the number of edges per node (or gene). The more edges a node has, the larger its size.

Fig. 2.

Hierarchical cluster by average and heat map of RSCU values of each codon in the SC-OGs of haemosporidian genomes. Each square in the heat map represents each codon RSCU value (in rows) within the SC-OG of each genome (in columns). Colors indicate the magnitude of RSCU values. A color bar indicates the species genome GC content.

Fig. 3.

Phylogenomic reconstruction based on synteny and graphical representation of the syntenic blocks across the plasmodium genus. Phylogenetic reconstruction based on synteny was inferred by maximum likelihood methods implemented in IQ-tree software (100 bootstrap replicates) from the synteny matrix obtained following the protocol of Zhao et al. (2021). The synthetic blocks were graphed with the R package GeneSpace (Lovell et al. 2022). The corrected assembly of P. coatneyi Hackeri is used here.

Fig. 4.

Mapping of genes involved in the parasitic stages of cell invasion. The phylogeny used corresponds to the species tree previously reported (Escalante et al. 2022). Each cell in the parasitic stages heatmaps corresponds to the number of gene copies for each gene per species. (*) Genes that are present but incomplete and (?) missing genes in the genome. The genes functions are described in Kaur et al. (2022), Graumans et al. (2020), and Wright and Rayner (2014) for the ookinete, sporozoite, and merozoite, respectively.

Fig. 5.

Species trees: a) phylogeny based on the concatenated alignment of the 1,961 SC-OGs using the Bayesian methods implemented in MrBayes v3.2.6 with the default priors (Ronquist and Huelsenbeck 2003) and the ML method in IQ-Tree (Minh et al. 2020). All nodes show posterior probabilities and bootstrap values as a percentage obtained for 1,000 pseudoreplicates. b) Phylogeny based on the multispecies coalescent model implemented in ASTRAL-III (Zhang et al. 2018a, 2018b) from the 1961 SC-GO trees. All nodes show values of posterior probabilities.

Fig. 6.

Time tree of the divergence of primate malarias using 110 genes. Divergence times were estimated using MCMCTree under the a) autocorrelated and b) independent rate models, using 3 calibration constraints that included a calibration for the origin of the Laverania clade. Calibrations priors were uniform, as explained in the text. Times are shown in MYA. 95% CrIs for the major clades are shown in parentheses next to the nodes.