The CCR5A32 allele as an HIV infection resistance marker: Possible evolutionary theories of origin

The CCR5A32 allele has been a focus of previous research in population genetics. This 32-bp deletion allele, present in heterozygous or homozygous genotype, allows for partial or complete resistance, respectively, to the R5 HIV strain infection. In a healthy human, CCR5 (C-C chemokine receptor 5) functions as a part of immune system, but in those who are exposed to HIV, it also acts as a co-receptor for the viral entry into the host cell. Individuals carrying the CCR5A32 are not capable of forming the functional CCR5 protein and the virus therefore cannot enter the host cell. This allele is also interesting because it occurs in European populations at the frequency of 10 % for the heterozygotes and 1 % for the homozygotes, but is essentially absent in other populations, which raised the question on how and when the allele originated and how it reached the current frequency variation. The estimated age of the allele allows for a spectrum of causative agents and historical events to be considered, including the Viking raids, smallpox infection, the Black Death (bubonic plague), and hemorrhagic fevers. Although many of these theories are now regarded as incorrect, we are summarizing them in the current historical review, along with the arguments that either support or advocate against their validity, in order to offer a chronological pathway of knowledge development related to this question.