Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele.
The high frequency, recent origin, and geographic distribution of the CCR5-Delta 32 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-Delta 32 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.
Galvani
Alison P
AP
Department of Integrative Biology, University of California, Berkeley, CA 94720, USA. agalvani@nature.berkeley.edu
Slatkin
Montgomery
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks; D005787:Gene Frequency; D005799:Genes, Dominant; D006678:HIV; D015658:HIV Infections / Q000235:genetics*; D006679:HIV Seropositivity; D006801:Humans; D007223:Infant; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D010930:Plague / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D012899:Smallpox / Q000235:genetics*; D013997:Time Factors
D019713:Receptors, CCR5