A mutant allele of the chemokine receptor CCR5 gene (CCR5-D32), which confers resistance to HIV-1 infection, is believed to have originated from a single mutation event in historic times, and rapidly expanded in Caucasian populations, owing to an unknown selective advantage. Among other candidates, the plague bacillus Yersinia pestis was implicated as a potential source of strong selective pressure on European populations during medieval times. Here, we report amplifications of the CCR5-D32 DNA sequence from up to 2900-year-old skeletal remains from different burial sites in central Germany and southern Italy. Furthermore, the allele frequency of CCR5-D32 in victims of the 14th century plague pandemic in Lü beck/ northern Germany was not different from a historic control group. Our findings indicate that this mutation was prevalent already among prehistoric Europeans. The results also argue against the possibility of plague representing a major selective force that caused rapid increase in CCR5-D32 gene frequencies within these populations. Genes and Immunity (2005) The human chemokine receptor CCR5 serves, together with CD4, as the principal coreceptor for macrophagetropic (R5) human immunodeficiency virus type 1 (HIV-1) strains. 1 A large number of genetic variants in the coding or the promotor region of the CCR5 gene have been identified in different ethnic groups. 2,3 Several of these naturally occurring mutations result in alterations of the receptor's amino-acid sequence and affect the ability of CCR5 to act as a chemokine receptor or HIV coreceptor. 4,5 The finding that nonfunctional receptor alleles are relatively frequent among different human populations has led to the hypothesis that a selective advantage might be associated with the loss of CCR5 function.The CCR5-D32 mutant, which is characterized by a 32-bp deletion in the gene segment encoding the second extracellular loop of the receptor, provides an instructive example of how host genetic variation may contribute to HIV-related pathology. Individuals homozygous for CCR5-D32 are almost completely protected against HIV-1 infection due to the absence of functional receptors from the cell surface. 6-8 Population surveys revealed a north to south gradient of CCR5-D32 allele frequencies of 16 to 3% across Europe and its absence in individuals of nonCaucasian descent. 9-11 Determination of the intrahaplotypic variation of flanking microsatellite loci in strong linkage disequilibrium with CCR5-D32 allowed calculation of the approximate age of the CCR5-D32 containing ancestral haplotype. Two different studies that analyzed separate microsatellite markers concluded that the CCR5-D32 allele originated from a single mutation event that took place in historic times approximately 700 years (95% confidence interval (CI): 275-1800) 11 to 3500 years (CI 400-13 000) 10 ago in northeastern Europe. Both studies assumed a heterozygote advantage of the CCR5-D32 mutant. The European locale and timing of the bubonic plague of the 14th century coincide with the calculat...

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Alternative models have been proposed to explain the formation and decline of the south Peruvian Nasca culture, ranging from migration or invasion to autochthonous development and ecological crisis. To reveal to what extent population dynamic processes accounted for cultural development in the Nasca mainland, or were influenced by them, we analyzed ancient mitochondrial DNA of 218 individuals, originating from chronologically successive archaeological sites in the Palpa region, the Paracas Peninsula, and the Andean highlands in southern Peru. The sampling strategy allowed a diachronic analysis in a time frame from approximately 800 BC to 800 AD. Mitochondrial coding region polymorphisms were successfully analyzed and replicated for 130 individuals and control region sequences (np 16021-16408) for 104 individuals to determine Native American mitochondrial DNA haplogroups and haplotypes. The results were compared with ancient and contemporary Peruvian populations to reveal genetic relations of the archaeological samples. Frequency data and statistics show clear proximity of the Nasca populations to the populations of the preceding Paracas culture from Palpa and the Peninsula, and suggest, along with archaeological data, that the Nasca culture developed autochthonously in the Rio Grande drainage. Furthermore, the influence of changes in socioeconomic complexity in the Palpa area on the genetic diversity of the local population could be observed. In all, a strong genetic affinity between pre-Columbian coastal populations from southern Peru could be determined, together with a significant differentiation from ancient highland and all present-day Peruvian reference populations, best shown in the differential distribution of mitochondrial haplogroups.

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