Nixing Malaria: DNA segment provides parasite resistance.

A section of the mosquito genome appears to give the insects a natural resistance to malaria, scientists report. Further analysis of that DNA might suggest new ways to prevent this deadly disease.

Most of the world's 300 million to 500 million annual new cases of malaria arise in sub-Saharan Africa. In that part of the world, the disease is mainly transmitted by a species of mosquito known as Anopheles gambiae. A mosquito picks up the malaria parasite, typically a protozoan called Plasmodiumfaleiparum, by biting people already infected with the disease.

Until recently, researchers had assumed that all A. gambiae could become infected with malaria. However, studies have shown that only a small percentage of those mosquitoes carry the parasite. Those findings led researchers to suspect that most mosquitoes have a genetic predisposition to fend off P.faleiparum, says microbiologist Kenneth Vernick of the University of Minnesota in Minneapolis-St. Paul.

To figure out which genes might be responsible for a mosquito's resistance to malaria, Vernick and his colleagues collected hundreds of female mosquitoes from the village of Bancoumana in Mali. After the captured insects laid eggs, the researchers raised the offspring to adulthood, then fed the bugs blood drawn from villagers who had malaria.

After giving the parasites several days to incubate inside their new insect hosts, Vernick's team dissected the mosquitoes and looked for telltale signs of malaria infection: tiny bags called oocysts, each of which holds thousands of developing parasites. Most mosquitoes had few or no oocysts in their guts. The others harbored varying numbers of the bags, with some of the bugs carrying hundreds of them.

Next, Vernick's team scanned the mosquitoes' DNA for markers that might correlate with a heavy oocyst presence. The researchers then narrowed their search to a segment of DNA that holds about 1,000 genes and eventually focused on two of these genes, APL1 and APL2.

When the team used a genetic technique to turn off APL2 in mosquitoes not previously exposed to the parasite, the change didn't alter the bugs' capacity to ward off malaria. However, turning off APL1 increased the number of oocysts in the insects about 10-fold, the scientists report in the April 28 Science.

Vernick notes that much more testing is required before scientists can confirm that APL1 plays a pivotal role in malaria resistance. But even if this gene doesn't determine mosquitoes' susceptibility to malaria, that function is almost certainly controlled by genes within the segment of DNA that he and his colleagues identified. "We've located this needle in a haystack," says Vernick. "Among 1,000 genes, we can test for the ones important in malaria resistance."

Researchers may eventually develop new malaria drugs on the basis of how malaria resistant mosquitoes fight off the disease, notes malaria researcher Matthew Hahn of Indiana University in Bloomington. However, he adds that Vernick's findings suggest that current efforts to engineer resistant mosquitoes might not work. "Most mosquitoes seem to be resistant to malaria, but people still get infected" he says.