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Fight against malaria grows more complicated


The parasite that causes human malaria is a more genetically diverse species than scientists had previously thought, and this could make it difficult to design an effective vaccine, according to a new study.

Vaccines target specific proteins in a parasite. If there is considerable variation between individual parasites, the vaccine may not be effective against the entire parasite population. Controlling only part of a population could select for parasites that are even more virulent.

Blood-feeding Anopheles gambiae mosquito. This mosquito is one of the leading malaria vectors in the world.

There has been considerable debate about Plasmodium falciparum's genetic diversity—which can also be used to calculate the parasite's age. Ancient organisms have had a longer period of time to accrue mutations in the genome, which often leads to more genetic diversity in species.

The researchers report that the most recent common ancestor of today's malaria parasite originated between 100,000 to 180,000 years ago. They analyzed about 200 genes in five parasites from South America, Central America, Southeast Asia, Africa, and Papua New Guinea.

The scientists found a high level of genetic variation among the P. falciparum samples. They identified 238 single nucleotide polymorphisms, the smallest changes in the genetic code, and 165 differences in genetic markers across the five samples. Xin-zhuan Su at the National Institutes of Health in Bethesda, Maryland led the study.

The research is "far larger" than previous studies and "provides strong evidence that P. falciparum is diverse enough to raise a greater challenge for public-health measures," writes Andrew G. Clark of Cornell University in Ithaca, New York in a News and Views article that accompanies the study in Nature.

In another study, researchers discovered that the gene that confers resistance to the commonly used anti-malarial drug chloroquine has moved quickly throughout the parasite population. The research was also led by Su and published in Nature.

Su and his team predict that chloroquine-resistance emerged independently in four different areas rather than of two locations according to previous estimates. They also found that the organism mutates rapidly, and therefore resistance to a particular drug can occur quickly.

In the study, researchers examined regions surrounding the gene pfcrt, which causes the malaria parasite's resistance to chloroquine. They studied more than 300 genetic markers on the chromosomes of 87 different parasites from throughout the world.

"The parasite eventually finds its way around drugs," says Jane Carlton, who collaborates to sequence the P. falciparum genome and leads two other sequencing projects of malaria parasites at The Institute for Genomic Research in Rockville, Maryland. "It mutates a gene in multiple places, and resistance to a combination of drugs can happen quickly."

The complete the sequence of Plasmodium falciparum will be published later this year.

See related GNN articles
»In the laboratory, fighting malaria with transgenic mosquitoes
»Genetic mutation protects against malaria

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Mu, J. et al. Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum. Nature 418, 323-326 (July 18, 2002).
Wootton, J.C. et al. Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature 418, 320-323 (July 18, 2002).

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