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Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike Epidemics
Simon Mead,1Michael P. H. Stumpf,2Jerome Whitfield,1,3Jonathan A. Beck,1Mark Poulter,1Tracy Campbell,1James B. Uphill,1David Goldstein,2Michael Alpers,1,3,4Elizabeth M. C. Fisher,1John Collinge1*
Kuru is an acquired prion disease largely restricted to theFore linguistic group of the Papua New Guinea Highlands, whichwas transmitted during endocannibalistic feasts. Heterozygosityfor a common polymorphism in the human prion protein gene (PRNP)confers relative resistance to prion diseases. Elderly survivorsof the kuru epidemic, who had multiple exposures at mortuaryfeasts, are, in marked contrast to younger unexposed Fore, predominantlyPRNP 129 heterozygotes. Kuru imposed strong balancing selectionon the Fore, essentially eliminating PRNP 129 homozygotes. WorldwidePRNP haplotype diversity and coding allele frequencies suggestthat strong balancing selection at this locus occurred duringthe evolution of modern humans.
1 Medical Research Council Prion Unit, and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK. 2 Department of Biology (Galton Laboratory), University College London, Gower Street, London WC1E 6BT, UK. 3 Institute of Medical Research, Goroka, EHP, Papua New Guinea. 4 Curtin University of Technology, Perth, WA, Australia.
* To whom correspondence should be addressed. E-mail: j.collinge{at}prion.ucl.ac.uk
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