近日，丹麦哥本哈根大学教授Simon Rasmussen及其研究团队报道了通过古今基因组追踪CCR5delta32缺失的进化史。相关论文于2025年5月5日发表于国际顶尖学术期刊《细胞》杂志上。
该课题组提供了一个详细的视角，通过时间和空间的删除的进化史。研究小组发现CCR5delta32等位基因出现在一个由84个变体组成的预先存在的单倍型上。利用这些信息，小组建立了一个单倍型感知概率模型，筛选了934个低覆盖率的古代基因组，并追溯了CCR5delta32缺失的起源，至少比现在（BP）早6700年。
此外，小组提供了强有力的证据，证明在距今8000年至2000年间，CCR5delta32单倍型在欧亚大陆西部发生了正选择，并表明该单倍型在拉丁美洲的存在可以用哥伦布发现新大陆后的遗传交换来解释。最后，该课题组人员指出了复杂的CCR5delta32基因型-单倍型-表型关系，在针对CCR5受体制定治疗策略时需要考虑这些关系。
据介绍，趋化因子受体变异CCR5delta32与HIV-1耐药性和其他疾病有关。它的进化历史和等位基因频率（10%-16%）在欧洲人群中有广泛的争论。
附：英文原文
Title: Tracing the evolutionary history of the CCR5delta32 deletion via ancient and modern genomes
Author: Kirstine Ravn, Leonardo Cobuccio, Rasa Audange Muktupavela, Jonas Meisner, Lasse Schnell Danielsen, Michael Eriksen Benros, Thorfinn Sand Korneliussen, Martin Sikora, Eske Willerslev, Morten E. Allentoft, Evan K. Irving-Pease, Simon Rasmussen
Issue&Volume: 2025-05-05
Abstract: The chemokine receptor variant CCR5delta32 is linked to HIV-1 resistance and other conditions. Its evolutionary history and allele frequency (10%–16%) in European populations have been extensively debated. We provide a detailed perspective of the evolutionary history of the deletion through time and space. We discovered that the CCR5delta32 allele arose on a pre-existing haplotype consisting of 84 variants. Using this information, we developed a haplotype-aware probabilistic model to screen 934 low-coverage ancient genomes and traced the origin of the CCR5delta32 deletion to at least 6,700 years before the present (BP) in the Western Eurasian Steppe region. Furthermore, we present strong evidence for positive selection acting upon the CCR5delta32 haplotype between 8,000 and 2,000 years BP in Western Eurasia and show that the presence of the haplotype in Latin America can be explained by post-Columbian genetic exchanges. Finally, we point to complex CCR5delta32 genotype-haplotype-phenotype relationships, which demand consideration when targeting the CCR5 receptor for therapeutic strategies.
DOI: 10.1016/j.cell.2025.04.015
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00417-9