[NYT] June 22, 2001 Genetic Study Dates Malaria to the Advent of Farming By NICHOLAS WADE Malaria, a leading cause of death in the world, is not the ancient affliction it might seem but a relatively recent scourge that dates only to the era when human societies first practiced agriculture. That is the conclusion of Dr. Sarah A. Tishkoff, a population geneticist at the University of Maryland, and a team of others in the field after analyzing DNA changes in a human gene that confers resistance to the malarial parasite. The changes can be dated to roughly 8,000 years ago in the case of a gene variant widespread in Africa and to roughly 4,000 years ago in the case of a second version of the gene common among peoples of the Mediterranean, India and North Africa. The finding is of interest to biologists trying to understand the pace of human evolution because it shows how quickly a variant gene that promotes its owner's survival can spread through a population. Dr. Tishkoff reported her finding in today's issue of the journal Science. Her work fits with several other pieces of evidence pointing to a recent origin for malaria. Last year two biologists noted from study of the malarial parasite that certain of its genes were very uniform in their DNA code, suggesting that the parasite's population had undergone a sudden expansion, maybe as recently as 5,000 years ago. That conclusion was controversial because malaria was assumed to be an ancient disease. One of the authors of the study, Dr. Francisco Ayala of the University of California at Irvine, said Dr. Tishkoff's finding was "music to my ears" because it pointed to a similar conclusion from the human side of the equation. One of the first scholars to propose that malaria had a more recent origin was a University of Michigan anthropologist, Dr. Frank B. Livingstone, who suggested in 1958 that the introduction of slash-and-burn agriculture in West Africa 3,000 years ago provided the first impetus for malaria to become common. The sunlit pools in the clearings would have been ideal breeding sites for the mosquitoes that carry the parasite, and the swelling human populations would have provided convenient hosts, Dr. Livingstone surmised. Some 300 million to 500 million cases of malaria occur each year, the World Health Organization calculates, and about two million people die of the disease. The human genome has adapted to the disease in various ways, notably by favoring changes in the genes that control the red blood cells, which the parasite invades, and the immune system. These adaptations include a variant hemoglobin gene that is protective when only one copy is inherited but causes sickle cell anemia in the relatively few people unlucky enough to receive the gene from both parents. The gene associated with sickle cell has been widely studied but not in the way necessary to date the origin of its variants. Dr. Tishkoff and her colleagues chose to examine a gene that conferred malarial resistance, one known as the G6PD gene (G6PD stands for glucose-6- phosphate dehydrogenase). Besides interest in malaria, a reason for Dr. Tishkoff's work was to study a human gene under intense selective pressure. Population geneticists usually prefer to study what are called neutral genes, because they accumulate regular random changes in their DNA, which serve as a useful genetic clock. But genes that have changed under the pressure of natural selection are in many respects more interesting, because they determine the track of human evolution and are likely to specify the differences between humans and their close cousin the chimpanzee. The dating of the G6PD gene's variants, done by a method worked out by a colleague of Dr. Tishkoff's, Dr. Andrew G. Clark of Pennsylvania State University, showed how rapidly a life-protecting variant of a gene can become widespread. The speed of genetic change may help explain several puzzles in human evolution. Kennewick Man, for example, the 10,000-year-old skeleton found in Washington State, is quite different from modern American Indians. Though some have speculated that the skeleton is a relic of an otherwise unknown arrival of Europeans, a simpler explanation is that American Indians evolved very rapidly, Dr. Ayala said. "We are morphologically so different in the different continents of the world," Dr. Ayala said. Dr. Tishkoff's work showing how rapidly the G6PD gene variants have spread may help explain how these differences could have occurred so quickly after humans began their expansion from Africa, as recently as 50,000 years ago, he said.
