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Malaria Parasite Genomes Shed Light on Organisms' Evolution

NEW YORK (GenomeWeb) – An international team of researchers has generated a new reference and new draft genome sequences for two less-common malaria parasites.

By comparing these new Plasmodium malariae and P. ovale genomes to the more prevalent P. falciparum genome and others, the researchers uncovered conserved and divergent genes among the parasites and traced the timing of the evolutionary splits between the lineages. The researchers also homed in on two previously unknown P. malariae gene families that resemble P. falciparum genes that are needed for entering human red blood cells. As they reported in Nature today, P. malariae and P. ovale only account for some 5 percent of malaria cases, about 10 million cases a year, but the parasites are harder to detect and kill.

"Although they are less lethal than Plasmodium falciparum, the rarer malaria species are likely to be much more difficult to eliminate," James McCarthy from QIMR Berghofer Medical Research Institute said in a statement. "These new genomes should now make it possible to develop improved diagnostic tools for these Plasmodium species, to ensure that drugs work against them and to assist vaccine development."

McCarthy and his colleagues used long-read sequencing to generate a P. malariae reference genome from clinically isolated samples. They assembled a 33.6-megabase genome estimated to carry 6,540 genes. At the same time, they generated draft genomes for both P. ovale curtisi and P. o. wallikeri, both of which were 33.5 Mb in size with 7,132 genes and 7,052 genes, respectively. The researchers also sequenced a parasite they dubbed P. malariae-like that they isolated from a chimpanzee.

P. malariae had lower levels of nucleotide diversity than P. malariae-like, similar to what's been observed in the human-infecting P. falciparum and its chimp-infecting relative P. reichenowi. This indicates that human-infecting parasites underwent recent population expansions, the researchers said.

However, they also found that P. brasilianum, which infects New World primates was indistinguishable from P. malariae, this suggesting that host adaptation in the P. malariae lineage is less strict than in the P. falciparum lineage.

With these new genomes, McCarthy and his colleagues constructed a maximum likelihood tree drawing on a dozen Plasmodium species. From this, they found that the split between P. ovale curtisi and P. o. wallikeri occurred some five times earlier than the split between P. falciparum and P. reichenowi. P. malariae and P. malariae-like, though, separated around the same time that P. falciparum and P. reichenowi did. A common historical event, then, might have contributed to speciation and host switching, they said.

P. malariae harbors two large gene families that hadn't before been detected. The proteins encoded by these gene families — fam-l and fam-m — resemble proteins that are exported by malaria parasite to the surface of red blood cells. In addition, a three-dimensional analysis of the protein structures further found that they resemble the P. falciparum RH5 protein, which is needed for erythrocyte invasion and has been a target of malaria vaccine development. Fam-l and fam-m might also have a role in adhesion, the researchers said.

"The genomes of these more neglected species will enable the development of tools to study malaria transmission and spread, which will be essential to achieve the goal of complete malaria eradication," co-author Thomas Dan Otto from the Sanger Institute said in a statement.