The evolution of genetic susceptibility to kuru

A very interesting article came out about a year ago by John Collinge’s group in the journal Philosophical Transactions of the Royal Society Biological Sciences that I just got around to reading (Mead, 2008).  The article focuses on  genetic susceptibility to kuru throughout the kuru epidemic.

Codon 129 of the prion protein gene (PRNP) affects several characteristics of prion diseases in general.  Heterozygosity at codon 129 (MV) confers a decrease in susceptibility to both acquired and sporadic forms of the illness.  Moreover, codon 129 affects age at onset, survival time, and incubation period.  Individuals with prion disease who are heterozygous at codon 129 generally have a longer incubation period in the acquired forms of the illness and also have a longer survival time (Brown, 1994) .  Also, all primary cases of variant CJD have been homozygous for methionine at codon 129.   The same is true of kuru, in that the vast number of individuals with prolonged incubation periods have been heterozygotes (Collinge, 2008).

The primary question of the paper is to ascertain whether or not codon 129 polymorphisms deviated from the norm in the Fore tribe during the kuru epidemic. 

The results are very interesting and are depicted in the below graphs.  For background, women were exposed to kuru throughout their lifetime during the epidemic whereas men were exposed as infants during the 1950’s.  During the epidemic, there was an higher proportion of heterozygotes than expected and it appears that the proportion of heterozygote individuals underwent a selection process during the epidemic due to kuru exposure.     

The authors conclude that kuru may have been responsible for the strongest episode of recent human balancing selection, which may have occurred at other points of time as well.  

1. Simon Mead et al., “Genetic susceptibility, evolution and the kuru epidemic,” Philosophical Transactions of the Royal Society B: Biological Sciences 363, no. 1510 (November 27, 2008): 3741-3746.
2. Paul Brown et al., “Human spongiform encephalopathy: The national institutes of health series of 300 cases of experimentally transmitted disease,” Annals of Neurology 35, no. 5 (1994): 513-529.
3. John Collinge et al., “A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea,” Philosophical Transactions of the Royal Society B: Biological Sciences 363, no. 1510 (November 27, 2008): 3725-3739.

del.icio.us Tags: kuru,evolution,genetics,selection,prion