Kuru Epidemic Summary

Jordan Haenel
10/12/15

Review: Genetic susceptibility, evolution and the kuru epidemic.
Simon Mead1, Jerome Whitfield1,2,3, Mark Poulter1, Paresh Shah1, James Uphill1, Jonathan Beck1, Tracy Campbell1, Huda Al-Dujaily1, Holger Hummerich1, Michael P. Alpers 1,2,3 and John Collinge1,

The most well documented case of human prion disease epidemic occurred in the early to mid-twentieth century in the isolated Eastern Highland region of Papua New Guinea. The Fore group was specifically affected as the kuru disease spread through ritualistic mortuary cannibalism and lead to a stark increase in the neurological disease in certain demographics within the population until 1960 when such practices ceased (Mead et al., 2008). Due to the high correlation
High selective pressure on the Fore population disrupted Hardy-Weinberg equilibrium resulting in increased resistance of the polymorphic PRNP gene. The genetic diversity within the Fore at the PRNP loci allowed for such changes to occur as age classes and gender participation varied, eventually leading to balancing selection within the Fore population after epidemic. This article is evidence of not only balancing selection within a human population as well as the most documented case of a human prion epidemic within an isolated population but also explores wide spread conserved polymorphisms within the human species and is a model of high levels of selection leading to evolution within a human population rapidly.

Prion diseases are the result of misfolded prion protein which post-translationally converts host cell prions into the coded misfolded protein leading to neurological diseases such as kuru (Wadsworth, 2008). These misfolded prion susceptibility can be inherited through the prion protein gene (PRNP) at the codon 129 conferring inheritable resistance as kuru prions are digested through mortuary
Some of the key aspects of balancing selection such as differentiation between populations as they deviate from the genome wide average, as well as polymorphisms segregating from frequencies and increased diversity around target of selection (Fijarczyk, 2015) are all satisfied. Balancing selection leads to increase of frequency of the heterozygous alleles, which is consistent with adaption to kuru within the fore, evidenced by the higher frequency of resistance in modern Fore as the population has adapted to the new lowered fitness of homozygosity as the epidemic emerged (Mead, 2008). There are more ways than just deviation from Hardy-Weinberg equilibrium to determine whether evolution is acting on a population, this is especially important when examining human populations, though the Fore are especially unique with their small population size, isolation and low migration rate which were subject to high selective pressures at the emergence of kuru. Heterozygote advantage seen in balancing selection evolution maintains polymorphisms, however the selection which varies in time, between sexes and life stages can all be considered factors in balancing selection as well as adaptation under high selective