Plugging away

SMACK! You’ve managed violently to halt a mosquito snacking on your blood. But how likely is it that the departed beastie was the kind that transmits malaria? The latest research shows that the answer has a lot to do with intimate details of the bug’s sex life.

There are a few hundred mosquito species in the genus Anopheles, but just a few are responsible for a great majority of the 600,000 annual malaria deaths. Most Anophelines are poor hosts for the Plasmodium parasites that cause the disease. But the differences between the dangerous mosquitoes and the merely annoying ones have remained unclear. That is changing, as the genetic and sexual particulars of Anophelines are laid bare.

In January a team led by Nora Besansky of the University of Notre Dame in Indiana published the genomes of 16 species, representing the full gamut of “vector capacity”—the ability to carry the malarial parasite. They painted a complex picture, reflecting much interbreeding over hundreds of thousands of years.

It took a bit of computational trickery, thanks to Robert Waterhouse, then of the Massachusetts Institute of Technology, to unpick that history. He helped to identify genes unique to each species and to begin to pick out those relevant to malaria. Anopheles gambiae, for instance—the mostly deadly strain—and its close cousins have recently gained 12 unique olfactory receptors. The genes for these may be evidence that A. gambiae has, quite literally, developed a taste for humans.

In a paper just published in Science, a subset of that same team, led by Flaminia Catteruccia of Harvard University’s Chan School of Public Health, reports yet more genetic variations, which they discovered by watching a great deal of mosquito sex.

The team examined nine Anopheline species from around the world—some harmless, and some that readily transmit malaria. The males of some species are known to deposit in the female a squishy “mating plug”, made up of their sperm, an enzyme called transglutaminase that makes the plug coagulate, and a hormone called 20-hydroxyecdysone, or 20E.

That hormone sets off a cascade of changes in the female. The most important, from the male’s point of view, is that it makes her less likely to mate again. From Plasmodium’s perspective, the more relevant effect is that it causes her to make more eggs, thereby diverting resources away from her immune system. That makes life easier for the parasite.

Dr Catteruccia and her colleagues found wide variations among their species in the degree of coagulation of the plug, and the levels of 20E within it. The relatively benign New World species Anopheles albimanus, for example, had no mating plug at all, and delivered a barely measurable dose of 20E. The four African and Indian species most known for their vector capacity had far higher levels of 20E and well developed, highly coagulated mating plugs.

The team referred to their book of genomes from January to map the historical development of such traits. For example, one copy of the gene for transglutaminase, which helps the mating plug coagulate, has evolved unusually quickly. Females have developed an egg-generating response to 20E in concert with males’ growing propensity to deliver it. In short, the sexual strategising of males and females in some species reflects exactly those conditions that are good for Plasmodium survival.

The findings are valuable clues in the battle against malaria; hijacking the hormone response, for example, could have maximal effect on only those species that pose the most danger. Intriguingly, two more genera of mosquitoes, Aedes and Culex, respectively responsible for Dengue fever and the West Nile virus, are also known to make use of seminal secretions that have onward effects on the female. The geneticists and the laboratory voyeurs may be busy for some time.