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Antibiotic-Resistance
Mosquitoes

The life cycle of the malaria parasite. Some of the merozoites form gametocytes, the sexual stage, which mate inside a mosquito, helping transmit malaria.

For a lowly parasite, the various species of protozoans in the genus Falciparum have lots of nasty tricks. They can

• change their coating to evade the immune system,

• be spread by mosquitoes -- a wily foe that no amount of insecticide can eliminate, and

• change the sex of their reproductive cells to promote survival.

Femme fatale
As you can see from the diagram, malaria has a confusing life cycle as its various forms move between female mosquitoes and vertebrate hosts -- people and animals.

The asexually formed "merozoites" kill red blood cells, which carry oxygen in the blood, causing disease symptoms. The sexual "gametocytes" infect new mosquitoes and spread the disease. When a female mosquito drinks blood from an animal with malaria, it slurps up gametocyces of both sexes. Inside the whiner, these specialized cells form "gametes" -- sex cells that mate to produce new parasites. Because malaria can't spread without this mating, understanding the ins and outs of the process may lead to controls for the disease.

Curiously, the ratio of female and male gametocytes changes during the infection of a vertebrate. In chicken malaria, for example, only 10 to 20 percent of gametocytes are male at first, but in birds that survive the disease, the sex ratio nears equality in a few days. A similar change also seems to occur in human malaria.

The rise in male gametocytes make sense, says Richard Paul, of the Pasteur Institute in Paris. The host's immune system, he explains, starts attacking the male gametocytes. The attack doesn't kill the cells, but it does slow them down, making it harder for them to find female gametes inside the mosquito (think protozoan wallflowers). Thus the parasite sends in an army of guyz to satisfy the gurlzz and ensure its survival.

Two major changes are happening during the change in sex ratios: the immune system is attacking the parasite, and new red blood cells are forming to replace those killed by malaria. Which effect -- if either -- causes the sex-change operation?

In recent research (see Sex Determination... below) Paul and his colleagues infected mice and chickens with malaria. Vaccinating the animals against the gametocytes did not affect the sex ratio, exonerating the immune system from blame for the changed sex ratio.

Blaming blood
Red blood cells were another story. Either depriving the chickens of oxygen or removing some of their blood caused the birds to form red blood cells abnormally early in the infection -- and changed the gametocyte sex ratio. Pinning down the cause, the researchers got the same result by injecting the hormone erythropoetin (EPO), which causes red blood cell formation. (Dirt-bag jocks use EPO to improve their performance by improving the blood's ability to carry oxygen.)

The researchers concluded that the hormone was signaling the parasite to change its behavior. "We think that the parasite uses the process of red blood cell production as a cue for producing more males, which will be becoming less efficient over time," Paul told The Why Files via email. "This is the first example of an animal (a protozoan) using hormonal cues of another organism (its host) to juggle or optimize its sex ratio."

Sexually frustrated parasite!
Eventually, the work could contribute to a smarter attack on malaria, which is rapidly gaining resistance to drugs and spreading dangerously after years on the wane. "This is just the beginning," Paul wrote. "If we can find out how sex is determined, then we might be able to turn all sexual forms male or female."

Knowing that the parasite juggles the sex of its gametes indicates that "sex determination is fundamental to the parasite," he adds. "Whether we can affect the ratio of males and females sufficiently we do not know, but at least we have something to work on."

Deer landlord
Although the research concerns the sex of reproductive cells, not whole animals, it's part of a larger effort to understand how organisms determine sex ratios.

In humans, sex is determined by the presence or absence of the Y chromosome. In wasps, sex is set when eggs are laid. In reptiles, the egg's environment plays a crucial role.

Environment also plays a role in red deer in Scotland. In a recent study (see "Population Density..." below) researchers found that population density and a mother's position in the "pecking order" both affected the ratio of males to females among red deer. Dominant mothers tend to have a higher ratio of fellas (and more total offspring), but when the population density rose, or stress on the mothers increased, the sex ratio changed. The researchers concluded that the influence of environment could explain contradictory results in studies of sex ratios.

-- David Tenenbaum

©2000, University of Wisconsin, Board of Regents.