Gene change link

Gene change in cannibals reveals evolution in action

• 14:27 19 November 2009 by Andy Coghlan
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It's a snapshot of human evolution in progress. A genetic mutation protecting against kuru – a brain disease passed on by eating human brains – only emerged and spread in the last 200 years.

When members of the Fore people in Papua New Guinea died, others would eat the dead person's brain during funeral rituals as a mark of respect. Kuru passed on in this way killed at least 2500 Fore in the 20th century until the cause was identified in the late 1950s and the practice halted.

Identification of kuru and how it was spread helped researchers identify how BSE – mad cow disease – spread through the feeding of infected cattle brains to other animals, and how this eventually led to variant Creutzfeldt-Jakob disease (vCJD), which has killed 166 people so far in the UK.

Simon Mead of the British prion research centre at University College London says the discovery of an "anti-kuru" gene is the most clear-cut evidence yet of human evolution in action.

"I hope it will become a textbook example of how evolution happens," he says. "It's a striking and timely example, given the 150th anniversary of the publication of Darwin's Origin of Species," he says.

Good mutations

Mead and his colleagues discovered the mutation after comparing stored DNA from 152 dead Fore victims of the disease with DNA from more than 3000 living Fore, including almost 560 who participated in the ritual eating of brains before it was banned.

In 51 survivors and their descendants, they discovered a hitherto-unknown variant of PRNP, the gene which makes prions, the proteins that spread the disease. These prions become malformed and in turn make all healthy prions they encounter malformed as well, in a chain reaction that ultimately destroys brains by turning them into a spongy mush.

The change in the gene comes at a position called codon 127. Throughout the animal kingdom, the codon contains the same amino acid, called glycine or "G", from each parent, giving the form G127G. To their astonishment, Mead and his colleagues found a variant of the codon never seen in nature before, in which one of the glycines has been swapped for a valine amino acid, giving the new variant the name G127V.

Initially, Mead and his colleagues thought that because the variant had never been seen before, it must have damaging rather than beneficial effects. "We thought we'd found the trigger for how kuru happens, that someone ate the brain of someone with the mutation and that's how the disease started spreading through the cannibalistic funeral feasts," he said.

"Instead, we found the complete opposite, which is that it was protective."

Inherited health

The mutation first arose about 200 years ago by accident in a single individual, who then passed it down to his or her descendants. "When the kuru epidemic peaked about 100 years back, there were maybe a couple of families who found that they and their children survived while all their neighbours were dying, and so on to today's generation, who still carry the gene," says Mead. "So it was a very sudden genetic change under intense selection pressure from the disease," he says.

None of the 152 victims of kuru had the protective gene, suggesting that it provides almost complete resistance to the disease. But it's not yet known whether the variant protects against other prion diseases. Mead said that experiments are already under way in mice deliberately given the new mutation, to see if they are protected against both kuru and vCJD.

Mead says that the team has evidence that the prion protein made by the new variant might prevent the abnormal version of the prion from multiplying, giving clues to how to treat or prevent vCJD with drugs.

In 2003, Mead and his colleagues discovered a much more common variant of the prion gene that provides protection against prion diseases. The variant's position in the gene, at codon 129, is just two units away from the new one.

The protective variant at codon 129 is called "MV", standing for the amino acids methionine and valine. All deaths except one from vCJD have so far been in people with the "MM" variant, suggesting that they are specially at risk.

Jose Ordovas, who studies genetics and nutrition at Tufts University, Boston, said the finding "really supports the concept of very rapid adaptation of humans to the environment".