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Transmission of prion diseases within and
between species is thought to involve the
consumption of contaminated meat. For
example, in the Fore tribe of Papua New
Guinea, an increase in ritual cannibalism
over the last century increased the
incidence of a human prion disease called
Kuru. When a government ban on cannibalism
was put in place 50 years ago, the frequency
of Kuru declined, although there are still
rare cases, because of the long incubation
times that are possible with prion diseases.
Previous work showed that individuals
heterozygous for a polymorphism that changed
a methionine to a valine in PrP were more
frequent than expected in Fore women,
suggesting that the homozygotes at this
polymorphism may be rare because they were
more likely to develop Kuru and die. This
prompted Mead et al. to examine the
frequency of this polymorphism in the PrP
gene (PNRP) in different populations.
They found methionine and valine alleles in
every population they studied, with the
highest frequency of the valine allele (55%)
in the Fore. Analysis of variation at other
polymorphic sites near the gene suggested
that this polymorphism was around half a
million years old, and had been maintained
in all populations since that time. The
PNRP gene also has an excess of
high-frequency polymorphisms and a deficit
of low-frequency polymorphisms when compared
with an expected distribution model with no
selection and a constant, or expanding,
population size. Together, these data showed
the action of balancing selection, or
'heterozygote advantage', on the PRNP
gene.
The best-known example of balancing
selection in humans is where heterozygotes
for sickle cell anaemia (commonly at a
glutamine/lysine polymorphism in beta
globin) show mild symptoms of sickle cell
anaemia but increased resistance to malaria.
Could there be a similar advantage at the
PNRP gene, with heterozygotes more
resistant to prion diseases? If so, the data
suggest that these prion diseases must have
been a significant cause of death during
human evolutionary history.
What prion diseases, and how were they
transmitted? The authors speculate that
cannibalism was widespread in the past,
providing ideal conditions for the
transmission of prion disease. There is some
archaeological evidence for this, such as
scratches and burn marks on Neanderthal
bones, and human muscle protein in preserved
human faeces (see Diamond, J. (2000)
Nature 407). However, it is also likely
that cross-species transmission occurred in
prehistory. Brains of scavenged carcasses
are nutritious, and only humans could use
tools to open the skull to get at the meat.
Furthermore, eating such tissue was the most
likely transmission method in the most
recent example of cross-species
transmission: when BSE in cattle became vCJD
in humans. |
