Malaria ranks among the world's most deadly infectious diseases. But a paper published online this week by Science  suggests it's a relatively young scourge of humankind. By tracing the history of mutations that protect against the disease, researchers have shown that malaria probably became a major problem less than 12,000 years ago, and only reached southern Europe a few thousand years ago.
Mutations in the gene for an enzyme glucose-6-phosphate dehydrogenase (G6PD) can cause bouts of severe anemia--a condition also known as favism, because eating fava beans often triggers the attacks. In the 1950s, researchers discovered that such defects are more common in areas where malaria is endemic. That suggested that, like sickle cell anemia and b-thalassemia, the mutations offer some protection against the disease and have been retained in the population. But for how long?
A team led by evolutionary geneticist Sarah Tishkoff at the University of Maryland, College Park, decided to trace back the origins of the deficiencies. They took blood from 747 people from North Africa, sub-Saharan Africa, and Europe, sequenced a short stretch of noncoding DNA within the G6PD gene, and let a computer program produce the most likely evolutionary history. They found that one form of the deficiency, which is prevalent in Africa, arose between 4000 and 12,000 years ago, suggesting that the rise of malaria there corresponded to the dawn of agriculture. Researchers have speculated that large pieces of forest were cleared around that time, creating more sunlit pools where malaria-transmitting mosquitoes could breed.
Another mutation, found predominantly in the Mediterranean, must have appeared between 1600 and 6600 years ago, indicating that malaria spread to Europe with Greek traders and travelers. Indeed, both Plato and Homer mention the appearance of a more severe form of a disease resembling malaria in the Mediterranean. "There are very few examples where you can correlate archaeology, genetics, and history," Tishkoff says.
"We know that malaria itself is a very old disease," comments Jonathan Friedlander, a biological anthropologist at Temple University in Philadelphia, "but we really didn't have a clue as to how long it has been a major factor in killing humans." He says the new study provides solid genetic evidence.