Dating the origin of the ccr5


Plague mortality was also assumed to affect all ages equally, consistent with historical accounts (22, 23).To assess selection generated by smallpox, we used the age distribution of smallpox burials in York between 17 (25) to parameterize smallpox mortality in the different age classes.Thus, the proportion of susceptible hosts within an age class , depends on the temporal pattern of disease transmission dynamics.Consistent with disease time series data, we assumed that smallpox mortality peaked every 5 years, although disease mortality between these peaks was still 25% of that during the peak years (25, 28).In addition, smallpox had a high case fatality rate of ≈30% (29, 30).


Our model incorporated the temporal patterns of smallpox and plague, respectively.Here, we investigate which disease is most likely to have generated the high frequency of We previously showed that age structuring of a host population can affect the selection of a resistance allele when the corresponding disease is responsible for significant mortality, particularly if disease virulence depends on host age and even more so if disease dynamics are episodic (31).Thus, here we use a population genetic framework that takes into account the temporal pattern and age-specific nature of different diseases.deletion allele together indicate that it has been intensely selected in Europe.

Although the allele confers resistance against HIV-1, HIV has not existed in the human population long enough to account for this selective pressure.

This allele provides almost complete resistance to HIV-1 in the homozygous state (4, 7, 12) and partial resistance with slower disease progression in the heterozygous state (4, 5, 8, 12).


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