Zhang Xinyi, Chen Yanhong, Liang Jingtong, Yang Yue, Chen Hui, Chen Zehui, Li Minhao, Chen Shuanghui, Chen Tingting, He Haopeng, Liu Yunsong, Liu Zhiyuan, Han Lu, Wu Dafei, Zou Zhengting, Qu Yanhua, Li Mingkun, Stoneking Mark, Fu Qiaomei, Xu Shuhua, Zeng Yi-Xin, Ma Liang, Liu Jianjun, Xu Miao, Zhai Weiwei
Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of the Chinese Academy of Sciences, Beijing 100049, China.
Natl Sci Rev. 2024 Nov 28;12(4):nwae438. doi: 10.1093/nsr/nwae438. eCollection 2025 Apr.
While Epstein-Barr virus (EBV) infection is ubiquitous globally, a high-risk EBV subtype associated with the extremely high incidence of nasopharyngeal carcinoma (NPC) was found in southern China, but the evolution history of EBV in humans and the origin of this high-risk subtype remains enigmatic. By obtaining one of the largest datasets of EBV genomes across the world, we found that EBV had an evolutionary history matching the out-of-Africa migration of humans. Within the high-risk subtype from southern China, we identified a rapidly expanding clonal strain originating from a recombination event between EBV strains from northern and southern Chinese around 4000 years ago, followed by strong Darwinian evolution with a fitness advantage of 4%. The clonal strain has almost doubled the risk for NPC compared to the high-risk subtype and explained around 66% of the NPCs, representing the highest risk factor for NPC identified so far. Taken together, we unraveled a strong co-evolution history between EBV and humans where human migration and admixture triggered subsequent recombination and expansion of a highly advantageous EBV strain, leading to a cancer epidemic in southern China.
虽然爱泼斯坦-巴尔病毒（EBV）感染在全球普遍存在，但在中国南方发现了一种与鼻咽癌（NPC）极高发病率相关的高危EBV亚型，然而EBV在人类中的进化史以及这种高危亚型的起源仍然是个谜。通过获取全球最大的EBV基因组数据集之一，我们发现EBV的进化史与人类走出非洲的迁徙相匹配。在中国南方的高危亚型中，我们鉴定出一种迅速扩张的克隆菌株，它起源于约4000年前中国北方和南方EBV菌株之间的重组事件，随后经历了强烈的达尔文进化，具有4%的适应性优势。与高危亚型相比，该克隆菌株使患NPC的风险几乎增加了一倍，并解释了约66%的NPC病例，是迄今为止确定的NPC最高风险因素。综上所述，我们揭示了EBV与人类之间强烈的共同进化史，其中人类迁徙和混合引发了一种高度有利的EBV菌株随后的重组和扩张，导致了中国南方的癌症流行。
