Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kurulike Epidemics
Abstract
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 balancing selection on the Fore, essentially eliminating PRNP 129 homozygotes. Worldwide PRNP haplotype diversity and coding allele frequencies suggest that strong balancing selection at this locus occurred during the evolution of modern humans.
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A balancing selection at the PRNP locus somewhat similar to what occurred in the Fore was discovered in some other world populations and has been interpreted as evidence of selection pressure from possible epidemics of prion diseases in prehistoric humans.
“Surprisingly, a balancing selection at the PRNP locus somewhat similar to what occurred in the Fore was discovered in some other world populations and has been interpreted as evidence of selection pressure from possible epidemics of prion diseases in prehistoric humans (40, 41).”
From Kuru (2012) · cites this paper as [40]
11 of 16 kuru cases that occurred in 1964-1988 had a 129 Val/Val genotype.
“Indeed, 11 of 16 kuru cases that occurred in 1964–1988 had a 129 Val/Val genotype (and unpublished data) (40–42).”
From Kuru (2012) · cites this paper as [40]
Kuru imposed a strong balancing selection on the Fore population.
“Kuru imposed a strong balancing selection on the Fore population (40).”
From Kuru (2012) · cites this paper as [40]
There was Hardy-Weinberg disequilibrium of the codon 129 genotype in a small cohort of older Fore women who had participated in multiple mortuary feasts.
“We previously reported that there was Hardy-Weinberg disequilibrium of the codon 129 genotype in a small cohort of older Fore women who had participated in multiple mortuary feasts.”
From A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure (2009) · cites this paper as [12]
In an earlier work, the authors proposed the theory that kuru imposed balancing selection on the Fore, acting at codon 129 of PRNP, although at the time they had sampled only 30 elderly exposed women.
“In an earlier work, we proposed the theory that kuru imposed balancing selection on the Fore, acting at codon 129 of PRNP, although at the time we had sampled only 30 elderly exposed women.12”
From A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure (2009) · cites this paper as [12]
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References 25 · Cited by 394
- Authors
- Mead, S., Stumpf, M. P. H., Whitfield, J., Beck, J. A., Poulter, M., Campbell, T., Uphill, J. B., Goldstein, D., Alpers, M., Fisher, E. M. C., & Collinge, J.
- Affiliations
- Curtin University (AU)
- Medical Research Council Prion Unit, and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK.
- Corresponding author
- Collinge, John
- ORCID
- Venue
- Science
- Published
- 2003-04-25
- Volume
- 300
- Issue
- 5619
- Pages
- 640-643
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2143113093
- Cited by
- 394
- References
- 25
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 11 · 2018: 4 · 2017: 22 · 2016: 8 · 2015: 16 · 2014: 16 · 2013: 14 · 2012: 23
- FWCI
- 12.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- kuru, prion disease, PRNP gene, balancing selection, Fore people, prion disease resistance, haplotype diversity, allele frequency, human evolution
- MeSH terms
- Adult, Animals, Cannibalism, Child, Codon, Disease Outbreaks, Ethnicity, Female, Gene Frequency, Haplotypes, Heterozygote, Homozygote, Humans, Immunity, Innate, Creutzfeldt-Jakob Syndrome, Kuru, Male, Methionine, Middle Aged, Mutation, Papua New Guinea, Polymorphism, Genetic, Selection, Genetic, Valine, Linkage Disequilibrium, PrPC Proteins, History, 19th Century, History, 20th Century, History, Ancient
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