New parasite genomes for malaria

Written byJennifer Evans

| 3 min read

More than linkurl:six years;http://www.the-scientist.com/article/display/13395/ after researchers sequenced the genome of the most virulent human malaria parasite, researchers now report the sequences of two more species, according to a pair of studies published in Nature this week. By comparing the genetics of Plasmodium falciparum to that of the newly sequenced species, P. knowlesi, and linkurl:P. vivax;, the two teams have begun to identify the different mechanisms by which each species maximizes its chances of evading the host immune system. "The genome sequence is important for laying the foundation for future studies," said linkurl:Elizabeth Winzeler,;http://www.scripps.edu/cb/winzeler/ a systems biologist at the Scripps Research Institute, who wrote an accompanying commentary to the studies. "The genome sequences [of P. vivax and P.knowlesi will now allow work in this area to go on that can advance biology relatively quickly." The majority of the 515 million annual cases of malaria are caused mainly by P. falciparum, primarily hitting populations in Africa, and P. vivax, prevalent in Asia, India, and South America. Since P. falciparum was sequenced in linkurl:2002,;http://www.ncbi.nlm.nih.gov/pubmed/12368864?ordinalpos=&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.SmartSearch&log$=citationsensor researchers have used the genetic information to identify targets for drug therapy and candidate genes for vaccines. Although P. falciparum is the most deadly of all Plasmodium species, P. vivax is a "more tenacious and tougher species [to eradicate]," explained linkurl:Jane Carlton,;http://www.med.nyu.edu/parasitology/faculty/jcarlton.html a genomicist at New York University and lead author of the P. vivax paper. The parasite can lie dormant in the liver, and can thus be unknowingly carried by a human host for several months or years, she said. To date, Carlton said, P. vivax has been the "linkurl:neglected species;http://www.ncbi.nlm.nih.gov/pubmed/18165478?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum of malaria" because it cannot be cultured and is difficult to isolate from patients in high enough quantities to study. Her group overcame this limitation by taking a human patient isolate and growing it in monkeys. Using their monkey model, they were able to isolate enough parasite material and DNA to sequence. "The identification of the P. vivax genome provides a tremendous resource for people who can't grow P. vivax in the lab," Carlton said. "We have to rely on sequences to push research forward." Comparing the P. knowlesi genome to that of P. falciparum, Carlton found that the species are similar in length and share more than two-thirds of their genes. The comparative analyses also demonstrated metabolic pathways that P. vivax shares with P. falciparum, "suggesting several ways P. vivax might be able to piggy-back off of current drug efforts in P. falciparum that target these pathways," she said. The researchers were unable to pointpoint candidate genes responsible for the dormant phase of P. vivax. Carlton said she was disappointed, but not surprised, as parasite dormancy likely has more to do with gene expression than the genes themselves. She said her group now plans to use the P. vivax sequence to do functional studies. P. knowlesi, a human-monkey parasite, is known to cause less of human malaria infections compared to P. falciparum and P. vivax, but the species is increasingly gaining recognition as an emerging public health problem in South-East Asia, said Arnab Pain, a genomicist at the Wellcome Trust Sanger institute and first author on the P. knowlesi paper. Pain and his team found that the location of P. knowlesi's multigene families involved in immune evasion were scattered throughout the chromosome, not the tips of chromosomes as in P. falciparum and P. vivax, suggesting its genome is much different from the two more prevalent species. The P. knowlesi sequence also contained sequences closely resembling the genes for two human proteins that regulate immune response. The parasite may trick its human host by mimicking its immune system proteins, Pain said, noting that the genes are absent from P. falciparum and P. vivax. Without the sequence, he said, "we would have never known [a species of the parasite] would show signs of molecular mimicry, a yet unknown biology of malaria."

New parasite genomes for malaria

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