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26 February 2007

Malaria: the bug that changed genes

Genes that began mutating thousands of years ago when confronted by the malaria virus have evolved over the centuries to actually protect humans from the deadly disease.

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Genes that began mutating thousands of years ago when confronted by the malaria virus have evolved over the centuries to actually protect humans from the deadly disease, a new study suggests.

The finding may lead to an understanding of how natural selection works to develop genetic protection and immunity against infectious diseases, according to lead author Sarah Ann Tishkoff, an assistant professor of biology at the University of Maryland.

Malaria, prevalent in tropical climates, is caused by a parasite transmitted to humans through the bite of a mosquito. It infects upwards of a 500 million people - and kills 2 million - each year.

"We looked at variations of the [gene] mutation that have appeared independently in several areas of the world where the incidence of malaria is high," Tishkoff says.

In each region studied, says Tishkoff, the mutation of the gene that protects against malaria appears to have "begun its anti-malaria development at about the same time history tells us malaria became prevalent in their respective areas."

"This is an example of how infectious disease can shape the path of human evolution," says Tishkoff.

"All genes are accumulating mutations, everywhere. Usually, people who have a mutation in a gene that's important for function die. But some of the genes are dragged along and maintained," Tishkoff explains.

"When the genes are found in such high frequency, then they are protective somewhere," she adds.

The international collaboration of researchers studied the genetic histories of people with the mutated gene in Africa, the Middle East, the Mediterranean, Europe and Papua New Guinea, all areas that have a high incidence of malaria.

In each area, say the researchers, "all subjects had the same variation of the G6PD (gene), which indicates the variations evolved independently from each other, likely as a response to selection resulting from malarial infection."

Through computer simulations, researchers estimated the rate of mutation, determined the age of the ancestral chromosomes and when the mutations began. They estimate Africa began to fall victim to the tiny parasite 6 500 years ago, while those in the Mediterranean area were affected 3 000 years later.

"There was a striking correlation in the distribution of the mutation and the distribution and frequency of malaria in the world. Every place with malaria had a high frequency of that mutation," says Tishkoff.

"I was amazed that the mutations occur on really distinct chromosome backgrounds in the Mediterranean and Middle East. It's unique, and you don't see it anywhere [else] in the world. But it's throughout that whole region, so it can be traced back to ancestral chromosomes. One person had that mutation," and it spread.

Researchers say that "by studying the ways that nature copes with devastating infectious diseases like malaria, we may be able to design more effective treatments or vaccines to protect people against these diseases."

Gene mutations found in complex human diseases, like diabetes, obesity and high blood pressure "are so common today," says Tishkoff. "But sometime in the past, there was some sort of selective benefits [to the mutations] that had a positive effect and made it easier to survive. For example, a gene mutation related to obesity might have developed because people needed to conserve their body fat to survive."

The findings correspond with evolutionary history, Tishkoff adds. "Ten thousand years ago, there was a climate change and the introduction of a mosquito that liked biting humans."

The malaria infections are tied in with civilizations, Tishkoff says. "When we went from hunter-gatherers to agriculturist and cities began to grow, people had enough food to stay in one place, and with that came the spread of infectious diseases. Our study ties the history and the archaeology to the genetics."

"This shows just how quickly the human genome can change. It's evolution in action," says Tishkoff. Quick, she adds, is a relative term when you consider the five million years that humans have roamed the Earth.

The findings appear in the current issue of Science.

Read more:
More on gene tests and your diet
Genetic shield for malaria

 
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