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Research: In sequence

3 January 2007

The first full sequencing of a clinical isolate of Plasmodium falciparum reveals potential targets for future antimalarial treatments.

Research into the genome of P. falciparum – which causes the most virulent form of malaria – usually relies on strains cultured in the lab. This is not ideal, however, as cultured strains do not necessary reflect the current state of the 'real-life' parasite; culturing can cause extensive loss or gain of DNA sequences, and strains may have been isolated from the wild before certain antimalarial drugs came into use.

Examination of isolates from patients with malaria can give a more accurate idea of how P. falciparum is evolving, but culturing clinical isolates is notoriously difficult. Now, researchers have sequenced the entire genome of a clinical isolate for the first time and without culture – by taking parasites directly from the patient.

The team, including Daniel Jeffares, Emmanouil Dermitzakis and Matthew Berriman from the Wellcome Trust Sanger Institute, compared the sequence of the clinical isolate and that of P. reichenowi (a close relative of P. falciparum that affects chimpanzees) with that of a cultured laboratory P. falciparum strain, to investigate how the parasite is evolving.

Among the most rapidly evolving genes identified in P. falciparum were those involved in host–cell interactions, including some surface antigens currently under investigation as antimalarial vaccine targets. Researchers hope that some of the as-yet-uncharacterised rapidly evolving genes may also be potential targets for antimalarial vaccines or drugs.

External link

Jeffares DC et al. Genome variation and evolution of the malaria parasite Plasmodium falciparum. Nat Genet 2007;39(1):120–5.

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