Using the distribution of the CCR5-D32 allele in third-generation Maltese citizens to disprove the Black Death hypothesis

Abstract

Malta was under Norman rule for over 400 years and has had three major documented plague outbreaks (and a number of minor ones) since the 14th century with death tolls of 5–15% of the population at the time. This makes the Maltese population ideal for testing the hypothesis that the Black Death (particularly that of 1346–52) was responsible for a genetic shift that spread the CCR5-D32 allele. By enrolling 300 blood donors to determine the percentage of the Maltese population resistant to HIV-1 (which uses the CCR5-receptor to infect cells), it was established that the CCR5-D32 allele frequency is almost zero in third-generation Maltese citizens and sequencing showed that the deletion observed in the region of interest is the 32-base deletion expected. Thus, despite the extensive Norman occupation and the repeated plague cullings, the CCR5-D32 allele frequency is extremely low. This provides a basis for the discussion of conflicting hypotheses regarding the possible origin, function and spread of the CCR5- D32 deletion