Evaluating plague and smallpox as historical selective pressures for the CCR5-Δ32 HIV-resistance allele

The high frequency, recent origin, and geographic distribution of the CCR5-Delta32 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. The prevailing hypothesis is that the selective rise of CCR5-Delta32 to its current frequency can be attributed to bubonic plague. By using a population genetic framework that takes into account the temporal pattern and age-dependent nature of specific diseases, we find that smallpox is more consistent with this historical role.