Milestones for Malaria: Parasite, mosquito genes decoded

About every 30 seconds, another child dies from malaria somewhere in the world. Two organisms, the parasite Plasmodium falciparum and the mosquito Anopheles gambiae, are responsible for most of those deaths. While feeding on human blood, the insect can infect people with the fatal parasite.

PARASITE POWER. In a complicated life cycle (illustration), the malaria-causing parasite Plasmodium falciparum (inset, bottom right, with 2-micrometer scale bar) goes through several stages in a mosquito species, such as Anopheles gambiae (inset, upper left). When an infected mosquito feeds, the parasite infects a person and then grows within the liver and blood. CDC and J. Gathany; Science; E.A. Levashina

In a dramatic convergence of research described in more than two dozen papers in the Oct. 3 Nature and Oct. 4 Science, hundreds of biologists announce that they have deciphered nearly the entire DNA sequence of the malaria-causing parasite and its insect partner. With the human, mosquito, and parasite genomes in hand, scientists express confidence that they’ll find novel ways to tackle the disease as they unravel the complex biology behind the parasite’s life cycle in mosquitoes and people.

“We are hopeful that this wealth of information will translate into new drugs, vaccines, and insecticides that will more effectively control malaria and, ultimately, lift a burden of suffering from millions,” says parasitologist Michael Gottlieb of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

Fotis Kafatos of the European Molecular Biology Laboratory in Heidelberg, Germany, suggests that knowledge of the insect’s and parasite’s genomes will also aid ongoing efforts to genetically engineer the mosquito so it can’t carry malaria-causing microbes (SN: 5/25/02, p. 324: Available to subscribers at Better Mosquito: Transgenic versions spread less malaria.).

Many biologists, however, caution that converting the newfound bounty of biological data into public health advances will take significant time and money. “Translating all of this information into new treatments and cures is not a trivial process,” Russell F. Doolittle of the University of California, San Diego in La Jolla concludes in one Nature commentary.

According to the initial analysis, A. gambiae has some 14,000 genes. That’s comparable to the number in the common fruit fly (SN: 6/10/00, p. 382).

More surprising, P. falciparum seemingly has just under 5,300 genes. Simple yeasts possess a similar number, even though P. falciparum lives a much more complicated life. It morphs into 10 forms and, at different life stages, dwells in people and mosquitoes.

“The number of genes doesn’t tell you the whole story about the biological properties of an organism,” says Malcolm Gardner of The Institute for Genomic Research (TIGR) in Rockville, Md., one of the leaders of the parasite-DNA-sequencing effort.

Citing similarities to genes of other organisms, investigators assigned probable functions to about 40 percent of P. falciparum‘s genes. “We still have an awful lot to learn about this parasite if we can only guess at the function of less than half the genes,” notes Gardner.

Still, authors of the new reports have identified novel parasite proteins that might prove useful for immunizing people against P. falciparum. They’ve also uncovered enzymes necessary for the parasite’s survival, which could be the targets of future antimalaria drugs.

In related work, TIGR scientists and their colleagues present the genome of another parasite, Plasmodium yoelii yoelii, which causes a malaria-like illness in rats but doesn’t infect people. TIGR’s Jane Carlton says that a side-by-side comparison of the genomes has begun to reveal what makes P. falciparum so deadly to people.

Malaria researchers are also celebrating the completion of the mosquito genome. In one of the reported studies, biologists observed increased activity of nearly 100 insect genes after A. gambiae obtained a blood meal. In another study, they compared the mosquito’s DNA with that of the fruit fly, documenting genetic differences between a blood-feeding insect and one that consumes rotting fruit. Despite the two insects’ many physical similarities, the DNAs of mosquito and fly differ more than do the DNAs of people and fish, the researchers conclude.

Other discoveries from the mosquito genome include

75 novel odorant receptors, proteins that the insect uses to sense airborne chemicals. Compounds that block the function of these receptors could prevent insects from detecting people, says Laurence J. Zwiebel of Vanderbilt University Medical Center in Nashville, whose team identified the sensory proteins.

76 gustatory receptors, proteins on the insect’s leg bristles that enable a mosquito to taste whatever it lands on. Studying these receptors may spawn new mosquito repellants that leave the insects with a bad taste when they settle on human skin, says Zwiebel.

More than 240 genes that have a role in the mosquito’s immune system, including ones that specifically combat parasites such as P. falciparum. Kafatos speculates that analyzing why only some strains of A. gambiae can ward off the parasite will reveal new ways to control the spread of malaria.

Zwiebel calls this week’s announcement of the mosquito and parasite genomes a watershed for malaria researchers. “All this genome information will keep me busy for the rest of my life,” he says.


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