Researchers discover genes that control regulatory functions in malaria mosquitoes

October 02, 2002

A team of scientists from the University of Georgia, using bioinformatics approaches, has discovered 35 genes that contain important regulatory peptides in Anopheles gambiae, the malaria mosquito. The new information could point toward ways to control the disease, which kills millions worldwide each year.

Included in the 35 are five genes that encode insulin-like peptides that probably have pivotal roles in the life cycle of the mosquitoes. An ability to interfere with the action of these genes on a large scale could keep the mosquitoes from passing on parasites that cause malaria.

"It is important to know as much as possible about how these insects transmit malaria," said Dr. Mark Brown, an internationally recognized mosquito biologist at UGA. "These genes offer new information on the regulatory processes that make the transmission of disease possible."

The research was published today in the journal Science and was funded by the National Institutes of Health.

Other researchers involved are Dr. Joe Crim and Dr. Stephen Garczynski of the department of cellular biology at UGA; Dr. Michael Riehle, an entomologist, like Brown, from the College of Agricultural and Environmental Sciences at UGA; and Dr. Catherine Hill of the University of Notre Dame.

Malaria is one of the planet's deadliest diseases and one of the leading causes of sickness and death in the developing world. According World Health Organization statistics from the late 1990s, there are 300 to 500 million clinical cases of malaria each year resulting in 1.5 to 2.7 million deaths. Children aged one to four are the most vulnerable to infection and death. Malaria is responsible for as many as half the deaths of African children under the age of five. The disease kills more than one million children--2,800 per day--each year in Africa alone. In regions of intense transmission, 40 percent of toddlers may die of acute malaria.

Anopheles, the African malaria mosquito, develops rapidly in water, and its reproduction cycle begins with successive blood meals from humans. Regulatory peptides acting as neurochemicals and hormones govern these processes in mosquitoes, so describing and understanding these peptides are crucial steps toward control.

"At this point the exact function of these genes is speculative," said Crim, a peptide-reception biologist. "None of these regulatory peptides was previously known for Anopheles. But their importance is clear."

The new study is part of an announcement made this week of a functional completion of the genome for Anopheles gambiae, an achievement by a number of laboratories that could have an enormous impact on future control of the Plasmodium parasites with which Anopheles infect humans with malaria.

The UGA team used bioinformatics-the study of gene databases on computers-to determine peptide-encoding genes in the Anopheles genome. Of particular importance was the elucidation of five insulin-like peptides. The scientists followed intriguing hints that Plasmodium appears to use insulin from either the female mosquito or the vertebrate blood meal for its own development, metabolism and reproduction. The importance of that connection could be crucial to understanding how the parasites are passed to humans and create disease.

"Since most peptide types exist as single-copy genes, each is a target for genetic interference," said Brown, "both to unravel regulatory functions and in the long-term to engineer Anopheles where it is less hospital for Plasmodium.

Crim said the computer program the team used looked for genetic sequences and identified candidates for regulatory genes. Though there may well be more than the 35 the team found, these are the most obvious and first targets for intervention. The completion of the A. gambiae genome is crucial to scientists, who can now compare genetic elements to other completed "gene maps" in species such as the fruit fly.

While uncovering genes and their locations on the chromosome, along with speculating on function, is important, more in-depth knowledge will be necessary before the researchers can find a way to make the mosquitoes less likely to deliver parasites that cause malaria. To this end, the scientists at UGA have begun to clone the genetic sequences and express them and will soon be able to determine their precise regulatory function in the mosquitoes, along with the receptors that allow the parasites to infect humans.

University of Georgia

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