Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution

Abstract

Elucidation of the evolutionary history and interrelatedness of Plasmodium species that infect humans has been hampered by a lack of genetic information for three human-infective species: P. malariae and two P. ovale species (P. o. curtisi and P. o. wallikeri)1. These species are prevalent across most regions in which malaria is endemic2,3 and are often undetectable by light microscopy4, rendering their study in human populations difficult5. The exact evolutionary relationship of these species to the other human-infective species has been contested6,7. Using a new reference genome for P. malariae and a manually curated draft P. o. curtisi genome, we are now able to accurately place these species within the Plasmodium phylogeny. Sequencing of a P. malariae relative that infects chimpanzees reveals similar signatures of selection in the P. malariae lineage to another Plasmodium lineage shown to be capable of colonization of both human and chimpanzee hosts. Molecular dating suggests that these host adaptations occurred over similar evolutionary timescales. In addition to the core genome that is conserved between species, differences in gene content can be linked to their specific biology. The genome suggests that P. malariae expresses a family of heterodimeric proteins on its surface that have structural similarities to a protein crucial for invasion of red blood cells. The data presented here provide insight into the evolution of the Plasmodium genus as a whole.

A Feast of Malaria Parasite Genomes

“…Data compiled from Ansari et al (2016) and Rutledge et al (2017). * indicates one or more assemblies generated from culture-adapted or chimpanzee/monkey-adapted strains. …”

“…Excitingly, the paper by Rutledge and colleagues in the January 2017 issue of Nature (Rutledge et al, 2017) does not disappoint and presents reference/high-quality drafts, as well as shotgun sequences, for five P. malariae , two P. malariae -like, three P. ovale curtisi , and two P. ovale wallikeri isolates (Table 1). For several of these, a means to identify pre-existing sequence data (“co-infection mining”) involved screening the sequencing reads of ~2,500 samples from the MalariaGen Pf3K global collection generated at the same genome-sequencing center, the Wellcome Trust Sanger Institute, where many of the authors are based.…”

“…First, the P. malariae genome appears to be indistinguishable from sequences of a species, Plasmodium brasilianum , found in New World primates, confirming a recent report describing them as a single anthrozoonotic species circulating freely between monkeys and humans in the Venezuelan Amazon (Lalremruata et al, 2015). Second, using 1,000 manually curated orthlogs in 12 Plasmodium species, Rutledge et al (2017) constructed maximum likelihood trees that appear to show rodent malaria parasites as an outgroup to P. ovale . This intriguing finding suggests that there was an ancestral host switch from primates to the ancestor of African thicket rats that host the rodent malaria species.…”

“…But multigene families tend to cluster in the repetitive, difficult-to-assemble subtelomeric regions of chromosomes, making it hard to tally gene numbers accurately. Rutledge et al (2017)’s use of long reads using the Pacific Biosciences next-generation sequencing platform, in combination with extensive manual curation, allows them to overcome that common obstacle and upgrade earlier analyses that were based on much lower-quality assemblies (Ansari et al, 2016). They quantitate large differences between P. ovale and P. malariae in gene complements of the pir , STP1 , and surfin families of surface/exported proteins and, most notably, discover two large, previously undistinguished gene families in P. malariae that they relate to a known P. falciparum RBC invasion protein using 3D protein modeling.…”

“…While the study by Rutledge et al (2017) provides missing pieces in the puzzle of the complex evolution and phylogeography of the Plasmodium genus, it also illustrates the benefits and drawbacks of sequencing laboratory-adapted strains versus extant clinical or field isolates. Whereas previous human malaria reference strains were chosen for sequencing because of their availability to researchers as pure frozen stocks from the Malaria Research and Reference Reagent Resource (https://www.beiresources.org/MR4Home.aspx) and the body of research describing them, this came at a cost.…”