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Scientists Produce Reference Genome for Plasmodium, Update Phylogeny

Wednesday, February 1, 2017

A new Nature paper from scientists at the Wellcome Trust Sanger Institute and other institutions delves into two Plasmodium genomes and reveals novel information about how these parasites have evolved. SMRT Sequencing was used to generate a reference genome and high-quality draft assembly for the organisms, providing a clear picture of species that have previously been difficult to characterize.

From lead author Gavin Rutledge, senior author Thomas Otto, and collaborators, “Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution” reports that prior studies have “been hampered by a lack of genetic information” for species responsible for many malaria infections.

The scientists deployed SMRT Sequencing to generate a reference-grade genome assembly for P. malariae; this new resource, they report, surpasses the quality of previous draft genomes. Measured in contiguity, the new assembly has just 63 scaffolds compared to more than 7,000 in previous drafts, with an N50 of 2.3 Mb, a dramatic improvement over the prior N50 of 6.4 kb. They also produced high-quality draft genomes for P. ovale and a parasite known as “P. malariae-like.”

These assemblies allowed for a better understanding of the phylogeny of these species, in some cases altering previous versions of the Plasmodium family tree. One such change indicates that the malaria parasite that infects rodents is more similar to P. ovale than to other strains that infect humans, suggesting that an ancestral host must have abandoned primates in favor of rodents. The scientists report that genes related to the invasion process evolve rapidly, contributing to host-specific adaptations. In addition, they write, “The relative dating of speciation events suggests that the move between non-human primates and humans occurred at approximately the same time in two well-separated lineages, suggesting that a common historical event may have promoted host switching and speciation in Plasmodium at the time.”

The team also found previously undiscovered gene content. “The most notable difference in the subtelomeres of P. malariae is the presence of two large gene families that were not apparent in earlier partial genome data,” they note. Proteins associated with these genes are thought to be important for binding to or entering red blood cells.

While this study represents an important advance in elucidating the parasite family with the new reference assembly, the authors call for continued work on this front. “Owing to the importance of rapidly evolving multigene families and genome structure, high quality genomes for all human infective species of Plasmodium are desperately needed,” they conclude.

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