Mosquito Genes are Discovered that Reduce Transmission of Malaria Parasite
NEW YORK, Oct. 2 - NYU School of Medicine scientists have for the first time identified genes in mosquitoes that reduce the natural transmission of the most lethal malaria parasite, a finding that potentially opens new avenues to preventing malaria, one of the world's greatest scourges.
In the October 4 issue of Science, the researchers report that they have discovered genes in naturally occurring populations of the mosquito, Anopheles gambiae, that enable the insects to resist infection by the malaria parasite, Plasmodium falciparum. The parasite is transmitted to humans though the bite of the mosquito.
"The new genes we have found are the first ones that make the Anopheles mosquito highly resistant to real, natural populations of the most deadly of the human malaria parasites, as opposed to laboratory parasite strains, and there are several ways this finding could help prevent transmission of malaria," says Kenneth Vernick, Ph.D., Associate Professor in the Department of Medical and Molecular Parasitology, who led the research.
It may be possible to spread the parasite-blocking genes among mosquito populations, and thereby deny the parasite enough mosquitoes to sustain itself in nature, says Dr. Vernick, and the genes might produce a parasite-killing compound that could be developed into a drug for human use.
The study appeared in a special issue of Science magazine in which scientists report that they have deciphered the entire genome of the Anopheles gambiae mosquito. Dr. Vernick was also a co-author on another paper in the issue that identified immune-related genes in the mosquito. Malaria is transmitted from person to person through the bite of female mosquitoes in the genus Anopheles, which carry malaria parasites. In order to sustain itself, the parasite must undergo a part of its lifecycle inside of the mosquito.
Dr. Vernick says that the genes that were found appear to have a large effect on the parasite's growth. In one case, mosquitoes with two copies of a parasite-blocking gene had an average of 0.2 parasites per mosquito, while insects with two copies of the alternate form of the gene, which makes insects susceptible to the parasite, had an average of 50 parasites per mosquito.
It isn't yet known how many parasite-blocking genes there are in the Anopheles mosquito, or how common these genes are in nature. Dr. Vernick estimates that at least half of the mosquitoes in natural populations may carry genes for resistance. Then why do they still transmit malaria? "It's likely that for many or most of the genes for resistance, the parasite develops its own 'counter-resistance' genes. There has been the general idea that the African malaria parasite and its mosquito vector were co-adapted, that is, they had arrived at a stable evolutionary relationship. Clearly, from our work, nothing could be farther from the truth.
"There is a high frequency of resistance genes in mosquitoes in nature, indicating that the parasite and the mosquito are in an intense evolutionary battle. The vector is trying to escape the parasite by developing a myriad of resistance mechanisms. The parasite, of course, doesn't want to go extinct, so it is permanently compelled to develop counter-measures to these mechanisms," says Dr. Vernick.
In addition to the genes that were found, the new study is novel because naturally occurring mosquitoes in a part of Africa where malaria is endemic were genetically screened in the laboratory.
The study took place in Mali in West Africa. Dr. Vernick and NYU colleague Frederick Odoul, Ph.D., Assistant Research Scientist, and Oumou Niaré, M.S., a graduate student from the University of Mali School of Medicine, collected some 5,000 mosquitoes that had bitten people infected with malaria, and counted the number of oocysts, one of the life stages of the malaria parasite, in the guts of the insects. They also extracted DNA from the insects to perform genetic tests. The mosquitoes that were analyzed were the offspring of wild mosquitoes from a village in Mali where malaria is endemic. Because female mosquitoes mate only once, the offspring analyzed in the study came from a single-pair mating that happened in nature. This approach insured that the results gave an accurate picture of the real mosquito genes that block the actual parasites currently infecting people in the endemic area.
The software used for the genetic analysis was designed by Kyriacos Markianos and Leonid Kruglyak from the Fred Hutchinson Cancer Research Center in Seattle, who are co-authors on the study. The software was designed to map the location on the mosquito's chromosomes of genes that influenced the number of parasitic oocysts.
Dr. Vernick's other co-authors include Jennifer Volz, Fotis Kafatos, Claudia Blass, and Rui Wang from the European Molecular Biology Laboratories in Heidelberg, Germany; and Abdoulaye Touré, Magaran Bagayoko, Djibril Sangaré, Sekou Traoré, Guimogo Dolo, Madama Bouaré, and Yeya Toure from the University of Mali School of Medicine in Bamako.
Genetic Loci Affecting Resistance to Human Malaria Parasites in a West African Mosquito Vector Population; O. Niaré et al.; Science 298, 213 (2002)