Bouwman Abigail, Shved Natallia, Akgül Gülfirde, Rühli Frank, Warinner Christina
1 Institute of Evolutionary Medicine, University of Zürich, Zürich, CH-8057, Switzerland.
2 Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA.
Hum Biol. 2017 Apr;89(2):119-124. doi: 10.13110/humanbiology.89.2.02.
The CCR5-Δ32 mutation present in European populations is among the most prominently debated cases of recent positive selection in humans. This allele, a 32-bp deletion that renders the T-cell CCR5 receptor nonfunctional, has important epidemiological and public health significance, as homozygous carriers are resistant to several HIV strains. However, although the function of this allele in preventing HIV infection is now well described, its human evolutionary origin is poorly understood. Initial attempts to determine the emergence of the CCR5-Δ32 allele pointed to selection during the 14th-century Black Death pandemic; however, subsequent analyses suggest that the allele rose in frequency more than 5,000 years ago, possibly through drift. Recently, three studies have identified populations predating the 14th century CE that are positive for the CCR5-Δ32 allele, supporting the claim for a more ancient origin. However, these studies also suggest poorly understood regional differences in the recent evolutionary history of the CCR5-Δ32 allele. Here a new hydrolysis-probe-based real-time PCR assay was designed to ascertain CCR5 allele frequency in 53 individuals from a 10th- to 12th-century CE church and convent complex in central Germany that predates outbreaks of the Black Death pandemic. High-confidence genotypes were obtained for 32 individuals, and results show that CCR5-Δ32 allele frequency has remained unchanged in this region of Central Europe over the last millennium, suggesting that there has been no strong positive selective pressure over this time period and confirming a more ancient origin for the allele.
欧洲人群中存在的CCR5-Δ32突变是人类近期正选择中最具争议的案例之一。该等位基因是一个32碱基对的缺失，使T细胞CCR5受体失去功能，具有重要的流行病学和公共卫生意义，因为纯合携带者对几种HIV毒株具有抗性。然而，尽管该等位基因在预防HIV感染方面的功能现已得到充分描述，但其人类进化起源却知之甚少。最初确定CCR5-Δ32等位基因出现的尝试指向14世纪黑死病大流行期间的选择；然而，随后的分析表明，该等位基因的频率在5000多年前就有所上升，可能是通过基因漂变。最近，三项研究确定了公元14世纪之前携带CCR5-Δ32等位基因呈阳性的人群，支持了其起源更为古老的说法。然而，这些研究也表明，CCR5-Δ32等位基因近期进化历史中存在一些尚未完全理解的区域差异。在此，设计了一种基于水解探针的新型实时PCR检测方法，以确定来自德国中部一座公元10至12世纪教堂和女修道院建筑群的53个人的CCR5等位基因频率，该建筑群早于黑死病大流行的爆发。获得了32个人的高可信度基因型，结果表明，在过去一千年中，中欧该地区的CCR5-Δ32等位基因频率保持不变，这表明在此期间没有强大的正选择压力，并证实了该等位基因起源更为古老。
