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DNA Sequencing Uncovers Global, Evolving Variations in Malaria Parasite Genome

NEW YORK (GenomeWeb) – An international team led by researchers at New York University's Center for Genomics and Systems Biology has used DNA sequencing to show how the malaria-causing parasite Plasmodium vivax evolves rapidly at a localized level to develop drug resistance.

More than 3.2 billion people are at risk of malaria infections, according to the World Health Organization. While P. vivax is the less deadly of the two dominant strains that causes illness in many parts of the world, it remains understudied. This is largely due to its diminished lethality and the difficulty of growing it in the laboratory.

However, P. vivax is becoming increasingly resistant to chloroquine, the first-line treatment, and the molecular mechanisms of resistance remain unknown, which has caused concern for many clinicians and researchers trying to eliminate the disease.

In a study published today in the journal Nature Genetics, the NYU-led team sequenced 182 DNA samples of P. vivax collected from patients in 11 countries, including Brazil, Colombia, India, Myanmar, Mexico, Papua New Guinea, Peru, and Thailand.

The scientists were able to separate P. vivax DNA from that of its human host, something that has been historically difficult, by using a set of unique 'sticky baits' that captured the parasite DNA and enabled the researchers to wash away the human DNA. Then, they sequenced the P. vivax genomes using the Illumina HiSeq 2000 or 2500.

After analyzing the reads, the researchers confirmed previous studies showing that P. vivax has high genomic diversity, but were able to determine how localized populations differed from one another.

"Plasmodium vivax is going to be the last malaria parasite standing," Jane Carlton, a professor in NYU's Department of Biology who led the study, said in a statement. "Our findings show it is evolving in response to anti-malarial drugs and adapting to regional differences, indicating a wide range of approaches will likely be necessary to eliminate it globally."

While each population of P. vivax was distinct, the researchers found that two genes, DHFR-TS and DHPS, are associated with antimalarial drug resistance that has swept through global populations. The researchers also identified several genes that adapted to regional differences in the human host and mosquito vector. One example is Pvs47, a gene involved in evasion of the mosquito immune response that enabled the species to successfully adapt to development and transmission in New World mosquito species.

"The DNA data show that P. vivax has clearly had a different history of association with global human populations than other malaria parasites, indicating that unique aspects of its biology may have influenced the ways in which it spread around the world," Daniel Neafsey, associate director of the Genomic Center for Infectious Disease at the Broad Institute and a senior author on the paper, said in a statement.

The researchers determined that Central and South American P. vivax populations are very genetically diverse and distinct from all other contemporary P. vivax populations. They believe this suggests that New World parasites may have been introduced by colonial seafarers and represent a now-eliminated European parasite population. 

In contrast they found that contemporary African and South Asian P. vivax populations are genetically similar, which they believe could be a result of South Asian populations genetically mingling with European lineages during the colonial era or, alternatively, a reflection of ancient connections between human populations in the Eastern Mediterranean, Middle East, and Indian subcontinent. 

The researchers noted that the relatively homogeneous genetic makeup of P. vivax in Mexico reflects a steady decline of the disease in this country over the last decade to under 10,000 cases. 

However, the Papua New Guinea population of P. vivax is very diverse relative to other P. vivax populations. The researchers said that this indicates the need to develop different methods of control in this region of the world.

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