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ShareApr. 11, 2003 — Human flesh may have been a fairly regular menu item for our prehistoric ancestors, according to researchers. They say it's the most likely explanation for their discovery that genes protecting against prion diseases -- which can be spread by eating contaminated flesh -- have long been widespread throughout the world.
The genes, which are mutant versions of the prion protein gene, show key signs of having spread through populations as the result of natural selection, the researchers report in the journal Science, published by the American Association for the Advancement of Science. Such mutations, or "polymorphisms," could have provided prehistoric humans a better chance of surviving epidemics of prion diseases, similar to modern day diseases such as Creutzfeld Jacob disease, or kuru.
"What we're showing here is evidence that selection for these polymorphisms has been very widespread or happened very early in the evolution of modern humans, before human beings spread all over the planet," said study author John Collinge of University College London. "We can't say which of those it is; but the obvious implication is that prion disease has provided the selection pressure."
Prion diseases are caused by misfolded versions of the prion protein, which cause other prion proteins to misfold and clump together in the brain. Kuru and Creutzfeld Jacob disease, in humans, as well as bovine spongiform encephalopathy, or BSE, in cows, cause brain degeneration and, ultimately, death.
In a previous study, Collinge and his colleagues determined that people with one normal copy and one mutated copy of the prion protein were somehow protected against Creutzfeld Jacob disease. The mutation consisted of a single amino acid substitution at a certain spot in the gene, and is known as "M129V." Among the Japanese and other populations in the Indian subcontinent and East Asia, a similar mutation called "E219K" has the same protective effect.
This phenomenon, in which heterozygotes have a better chance of survival than homozygotes, is called "balancing selection." (A possible explanation in this case may be that the uniform prion proteins of homozygotes clump together more easily in the brain, increasing the chance of disease in contrast to those of heterozygotes.)
"There are only a handful of examples of genes thought to be under balancing selection. They are thought to offer protection against infectious disease," Collinge said.
From approximately 1920 to 1950, a kuru epidemic devastated the Fore in the Highlands of Papua New Guinea. At mortuary feasts, kinship groups would consume deceased relatives, a practice that probably started around the end of the 19th Century, according to local oral history. The Australian authorities imposed a ban on cannibalism there in the mid-1950s.
The same genetic variation in the prion protein that helps protect against Creutzfeld Jacob disease turned out to do the same for kuru. Studying Fore women who had participated in mortuary feasts, Collinge's group found that 23 out of the 30 women were heterozygous for the prion protein gene, possessing one normal copy and one with the M129V mutation.
The researchers sequenced and analyzed the prion protein gene in more than 2000 chromosome samples from people selected to represent worldwide genetic diversity. They found either M129V or E219K in every population, with the prevalence decreasing in East Asia (except for the Fore, who have the highest frequency in the world).
Collinge's team also studied the diversity of sequence variations in a block of DNA containing the prion protein gene, in European, African, Japanese, and Fore populations. The prevalence of the M129V and E219K variations, even when the sequence at other spots was highly variable, indicated that the variations were ancient--more than 500,000 years old, according to authors' estimates.
Finally, the researchers identified a telltale signature of balancing selection in the gene: a greater than average number of highly variable sites, and a smaller than average number of low-frequency variations.
These findings are consistent with other lines of evidence indicating that prehistoric populations practiced cannibalism, such as cuts and burn marks on Neanderthal bones, and biochemical analysis of fossilized human feces.
"There is extensive anthropological evidence that cannibalism is not just some rarity that happened in New Guinea," Collinge said.
Collinge's co-authors are Simon Mead, Michael Stumpf, Jerome Whitfeld, Jonathan Beck, Mark Poulter, Tracy Campbell, David Goldstein, Michael Alpers, and Elizabeth Fisher of University College London, in London, U.K. Jerome Whitfeld is also at the Institute of Medical Research, in Papua New Guinea. Michael Alpers is also at the Institute of Medical Research, in Papua New Guinea, and Curtin University of Technology, in Perth, Australia.
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