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Sep 7, 2012

Five Malaria Genomes Sequenced

  • Scientists have sequenced the entire genomes of five Plasmodium vivax strains taken from the blood of patients on different continents, providing a wealth of new data to help in the future mapping of malarial parasite traits such as drug resistance, and determine how different strains are geographically distributed. The work, by researchers at Case Western Reserve University and the Cleveland Clinic Lerner Research Institute, has identified over 80,000 SNPs that can form the basis of association studies and population surveys to study the diversity of P. vivax in a single region.

    Critically, the results also demonstrate that P. vivax isolates from patients in Madagasar, Cambodia, and South America are genetically surprisingly similar, and exhibit little evidence of local adaptation. One possibility for the relative lack of genetic diversity is that the P. vivax population has only recent origins, and has just dispersed rapidly across the world without major loss of diversity or influence from natural selection. A second possibility for the observed allele sharing, however, is that there’s been a continuous gene flow in the current P. vivax population. “P. vivax is now a cosmopolitan parasite that can be easily spread throughout the world by way of dormant hypnozoites,” the investigators suggest.

    “If this second hypothesis is true, it holds bleak prospects for P. vivax malaria elimination,” the researchers add. “With high level of gene flow, genetic polymorphisms conferring drug resistance or novel invasion mechanisms could spread across the world and further complicate control strategies.”

    The reported work is the result of sequencing three P. vivax strains taken from patients in Cambodia, two from infected individuals in Madagascar, and a South American human strain that has adapted to survive in monkeys. The researchers also resequenced the Sal I strain, which originated from a patient in El Savador in 1972, and was the first P. vivax strain to have been sequenced, back in 2008. Sal I resequencing effectively allowed the researchers to confirm the viability of their next-generation whole-genome sequencing approach.

    P. vivax is the most frequently transmitted and widely distributed malarial parasite worldwide, with estimates suggesting it causes some 250 million cases of the disease every year, resulting in a global public health burden of some $1.4–4 billion. The ability to sequence P. vivax taken directly from patients represents a major achievement as the parasite doesn’t survive in vitro, which makes functional studies difficult, and previous genetic analyses have centered on the dozen or so strains that can be propagated in monkeys. However, further study of the parasite is vital both for understanding the malarial disease process, identifying possible therapeutic strategies, and understanding how different strains adapt and spread.

    Drs. Zimmerman et al., describe their work in PLoS Neglected Tropical Diseases in a paper titled “Whole Genome Sequencing of Field Isolates Provides Robust Characterization of Genetic Diversity in Plasmodium vivax.”


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