中国人民解放军军事医学科学院崔玉军小组的最新研究提出了通过242个全基因组重排分析鼠疫耶尔森氏菌的进化。相关论文于2025年8月4日发表在《自然—遗传学》杂志上。

该课题组研究人员开发了一种双重验证策略来分析来自不同种群的242个鼠疫杆菌天然分离物的完整基因组。研究组检测到459个重排，这增强了系统发育分辨率，并解决了第三次大流行的多灶性。重排主要由它们共同的插入序列介导，其中IS1661和IS100表现出最高的活性。rpsO-pnp操纵子的43个热点和趋同进化证明了这些重排是在强烈的正选择下进行的，它们的破坏和重连接改变了基因的表达和温度胁迫反应。

课题组研究人员还发现了人类无毒系统群中独特的结构变化，使3个基因失活，并重新排序了17个基因间区域，其中一些影响毒性相关基因。本研究为鼠疫杆菌的进化提供了新的视角，揭示了实验靶点，并建立了一种研究频繁重排微生物的方法。

据悉，鼠疫耶尔森氏菌是引起鼠疫的细菌，它具有动态基因组，其高度保守的片段易于重排，影响基因功能和进化。然而，了解这些模式受到少数完整基因组和分析方法的限制。

附：英文原文

Title: Insights into Yersinia pestis evolution through rearrangement analysis of 242 complete genomes

Author: Wu, Yarong, Yang, Chao, Mu, Kai, Guo, Yan, Song, Yajun, Yang, Ruifu, Cui, Yujun

Issue&Volume: 2025-08-04

Abstract: Yersinia pestis, the bacterium that causes the plague, has a dynamic genome with highly conserved fragments prone to rearrangement, influencing gene function and evolution. However, understanding these patterns is limited by few complete genomes and analytical methods. We developed a dual-validation strategy to analyze 242 complete genomes of Y. pestis natural isolates from diverse phylogroups. We detected 459 rearrangements, which enhanced phylogenetic resolution and resolved the third pandemic’s polytomy. Rearrangements are primarily mediated by four common insertion sequences, with IS1661 and IS100 showing the highest activity. These rearrangements are under strong positive selection, evidenced by 43 hotspots and convergent evolution in the rpsO-pnp operon, whose disruptions and reconnections altered gene expressions and temperature stress responses. We also identified unique structural alterations in human avirulent phylogroups, inactivating three genes and reordering 17 intergenic regions, some affecting virulence-related genes. This study provides a fresh perspective on Y. pestis evolution, revealing experimental targets and establishing a methodology for microbes with frequent rearrangements.

DOI: 10.1038/s41588-025-02264-5

Source: https://www.nature.com/articles/s41588-025-02264-5