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Oct 8, 2008

P. vivax and P. knowlesi Genomes Decoded

  • Separate groups of researchers have sequenced the genomes of Plasmodium vivax and the lesser known malaria parasite, Plasmodium knowlesi. Both studies are published in the October 9 issue of Nature.

    Jane Carlton, Ph.D., NYU Langone Medical Center, led about 40 researchers from across the world in the efforts to sequence P. vivax. They report that the genome for P. vivax is dramatically different from the genomes of three other sequenced malaria parasites: different in content, structure, and complexity.

    Yet, the P. vivax genome was found to be far more similar to that of P. falciparum than was expected, according to investigators from the Barcelona Centre for Research on International Health. The study revealed 150 genes specific to P. vivax.

    The genome analysis also indicated that P. vivax should have alternative mechanisms for infecting the erythrocytes. These alternative routes have not been observed, but the scientists note that the the genetic information necessary for this to happen is written in the genome.

    The investigators used whole genome shotgun methods in this research and plan to sequence six other P. vivax genomes from Brazil, Mauritania, India, North Korea, and Indonesia.

    Separately, a group led by scientists at the New York University School of Medicine and the J. Craig Venter Institute sequenced the P. knowlesi genome. The work revealed it to be an example of molecular mimcry, likely a major factor in survival. The team also found several members of a large gene family that contain sequence signatures similar to a human gene involved in regulation of the regulation of the immune system. The parasite versions of the human protein are thought to interfere with recognition of infected red blood cells, according to the researchers.

    They also found that P. knowlesi has a fundamentally different architecture of the genes involved in antigenic variation compared to other malaria parasites. “Unusually, the key genes that we think help the parasite to evade detection and destruction by host defenses are scattered through the genome,” points out to Arnab Pain, Ph.D., project manager at the Wellcome Trust Sanger Institute. “In the other species we have examined, these genes are most often near the tips of the chromosomes.”

    The genome sequence, the scientists state, provides an updated catalogue of proteins that help the parasite in the early stages of infection. They identified novel regions in the genome that help to understand the regulation of these key genes and the transport of their proteins to the red cell surface.



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