Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike Epidemics

@article{Mead2003BalancingSA,
  title={Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike Epidemics},
  author={Simon Mead and Michael P. H. Stumpf and J T Whitfield and Jonathan Beck and Mark Poulter and Tracy A. Campbell and James B. Uphill and David Goldstein and Michael P. Alpers and Elizabeth M. C. Fisher and John Collinge},
  journal={Science},
  year={2003},
  volume={300},
  pages={640 - 643}
}
Kuru is an acquired prion disease largely restricted to the Fore linguistic group of the Papua New Guinea Highlands, which was transmitted during endocannibalistic feasts. Heterozygosity for a common polymorphism in the human prion protein gene (PRNP) confers relative resistance to prion diseases. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are, in marked contrast to younger unexposed Fore, predominantly PRNP 129 heterozygotes. Kuru imposed strong… 
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A novel protective prion protein variant that colocalizes with kuru exposure.
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Variants at codons 127 and 129 of PRNP demonstrate the population genetic response to an epidemic of prion disease and represent a powerful episode of recent selection in humans.
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TLDR
A model that combines the dynamics of kuru transmission and the population genetics of human resistance indicates that human resistance arises from a combination of both a longer incubation period and reduced susceptibility to infection.
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Using the well‐characterized, human diversity sample series, we show that the V129 prion allele has a very high frequency in South American populations relative to the East Asian populations from
Molecular evolution of the sheep prion protein gene
  • J. Slate
  • Biology
    Proceedings of the Royal Society B: Biological Sciences
  • 2005
TLDR
The molecular evolution of PRNP in ruminants is examined and it is shown that variation in sheep appears to have been maintained by balancing selection, a profoundly different process from that seen in other ruminant.
Genotyping of PRNP coding region for scrapie in Indian sheep
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Polymorphisms of the prion protein gene at the codons responsible for the susceptibility and resistance of the scrapie disease in the sheep are identified and absence of ARR allele in the Mandya sheep should be taken into consideration for the implementation of a preventive selection programme to avoid erosion of the genetic stock.
Negative Purifying Selection Drives Prion and Doppel Protein Evolution
TLDR
Overall, the results clearly indicate that both proteins are under strong selective constraints with relaxed selection on amino acid residues connecting α-helices 1 and 2.
The prion protein gene in humans revisited: lessons from a worldwide resequencing study.
TLDR
The analyses reveal the worldwide pattern of variation at the PRNP gene to be inconsistent with neutral expectations, indicating instead an excess of low-frequency variants, a footprint of the action of either positive or purifying selection.
Kuru: Genes, Cannibals and Neuropathology
TLDR
Kuru was the first human transmissible spongiform encephalopathy or prion disease identified, occurring in the Fore linguistic group of Papua New Guinea, and formed a background against which the recent epidemics of iatrogenic and variant Creutzfeldt-Jakob disease could be studied.
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