Spread of farming may have given rise to the biggest killer in human history

Malaria became the biggest killer in human history after the invention of agriculture in about 8,000BC, according to scientists who have found evidence to suggest that the rise of the disease can be attributed to the spread of farming.

The scientists believe malaria was not a major problem prior to the introduction of agricultural techniques that led to new mosquito breeding sites and a rise in human population density.

A study of the human genes that confer limited immunity against the malaria parasite has found that a mild form of the disease arose in tropical Africa about 10,000 years ago, but it was only after the introduction of farming in the Middle East that the disease took a more lethal turn.

Malaria, caused by a microscopic blood parasite transmitted in a mosquito's bite, infects about 500 million people each year, killing about 2 million.

The disease has helped to shape human history by decimating invading armies and making certain places difficult to colonise. West Africa became known as the "white man's grave" at the time of the British Empire because of malaria.

A team led by Professor Sarah Tishkoff of the University of Maryland has analysed mutations in a human "housekeeping" gene called G6PD, which is normally involved in metabolising glucose but which, when mutated, can confer limited protection against infection with Plasmodium, the malaria parasite.

The G6PD gene study was pioneered by Tom Vulliamy and Lucio Luzzatto at Hammersmith Hospital in London. They analysed how mutations in the gene caused metabolic disorders in people of Mediterranean or African origin.

Although such mutations can cause fairly serious problems for people in modern society, their high prevalence within an ethnic group suggests they must have provided some advantage in the past – notably malaria resistance.

Professor Tishkoff's study, published in the journal Science, found that two mutations in the G6PD gene almost certainly arose as a result of the emergence of malaria.

Professor Tishkoff said: "We looked at variations of the mutation that have appeared in several areas where the incidence of malaria is high. In each region, the mutations in G6PD appear to have arisen at about the same time that malaria become prevalent."

One of the mutations arose in Africa between 3,840 and 11,760 years ago and the other arose in the Mediterranean region between 1,600 and 6,640 years ago, the professor added.

Between about 7,000 and 12,000 years ago, a dramatic change in the climate of Africa increased temperatures and humidity, creating sunlit pools of water in which mosquitos could breed.

At about the same time, agriculture in the Middle East and north-east Africa led to forest clearing in the Mediterranean region and the creation of mosquito-breeding pools. With a growing population living in dense villages, the conditions were ripe for a more lethal form of malaria to spread fast.

Professor Tishkoff believes the second mutation arose in the Mediterranean area as a result of the emergence of a deadlier form of malaria, which may have been introduced by Greek farmers and spread throughout Asia by the army of Alexander the Great.

"By studying how nature copes with malaria, we may be able to design more effective treatments," the professor said.