鼠疫耶尔森菌低毒种群基因组多样性和选择压力分析

doi:10.16288/j.yczz.25-318

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Hereditas(Beijing) ›› 2026, Vol. 48 ›› Issue (8): 828-841.doi: 10.16288/j.yczz.25-318

• Research Article • Previous Articles Next Articles

Genomic diversity and selection pressure analyses of low-virulence Yersinia pestis lineages

Jiayi Zhang¹^,²(), Yihua Jia²^,³, Kai Mu², Mengnan Cui², Haifeng Pan¹, Yujun Cui¹^,²(), Yarong Wu²()

¹ School of Public Health, Anhui Medical University, Hefei 230032, China
² State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China
³ School of Pharmacy, Suzhou Medical College, Soochow University, Suzhou 215000, China

Received:2025-12-03 Revised:2026-02-06 Online:2026-08-20 Published:2026-02-27
Contact: Yujun Cui, Yarong Wu E-mail:2345010442@stu.ahmu.edu.cn;cuiyujun.new@gmail.com;wuyarong525@126.com
Supported by:
National Key Research and Development Program of China(2024YFC2310100);National Natural Science Foundation of China(32500006)

Abstract

Abstract:

Yersinia pestis, the causative agent of plague, is a highly virulent pathogen that has caused three historical pandemics and currently persists in multiple active natural foci worldwide, posing a serious threat to human health and public safety. Distinct phylogenetic lineages of Y. pestis exhibit differences in virulence, among which the Microtus biovar within the 0.PE4 lineage is nearly avirulent to large mammals. Comparative genomics between low-virulence and highly virulent populations is therefore key to elucidating the evolutionary basis of virulence. However, comprehensive population-genomic analysis of the low-virulence lineage remains limited, particularly those integrating multiple types of genomic variations. In this study, we analyzed 169 low-virulence strains and 215 representative high-virulence strains collected from long-term national surveillance data in China and public databases. Phylogenetic and spatiotemporal analyses revealed geographic clustering within the low-virulence 0.PE4 lineage. The 0.PE4.3 subclade circulating in China and Mongolia was further subdivided into three regionally associated tertiary lineages, with two more finely resolved quaternary lineages identified specifically in Inner Mongolia. Comparative genomic analyses with representative high-virulence genomes identified mutations fixed in the most recent common ancestor (MRCA) of the low-virulence population and its subclades. Among these, 81 single nucleotide polymorphisms (SNPs), 19 insertion and deletions (Indels), and 5 large fragment losses are shared by all low-virulence strains, defining the genomic features of their MRCA. Together with selection pressure analysis, we identified five genes (ail, rovA, tssH, cdiA, and alr) under strong positive selection, which are involved in virulence, metabolism, and adaptation. Collectively, this study reconstructs the phylogenetic topology of the global low-virulence Y. pestis population and identifies key genomic variations that occurred during its evolutionary process, providing valuable insights for fine-scale tracing and identifying potential molecular targets for elucidating virulence mechanisms.

Key words: Yersinia pestis, virulence, low-virulence lineage, phylogenetic analysis, comparative genomics, selection pressure

Jiayi Zhang, Yihua Jia, Kai Mu, Mengnan Cui, Haifeng Pan, Yujun Cui, Yarong Wu. Genomic diversity and selection pressure analyses of low-virulence Yersinia pestis lineages[J]. Hereditas(Beijing), 2026, 48(8): 828-841.

Figures/Tables 6

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变异	突变类型	突变个数	占比(%)	总计*
SNP	同义突变	131	20.66	634
	非同义突变	332	52.36
	无义突变	18	2.84
	间区	153	24.13
Indel	移码突变	775	57.75	1,342(1,329)
	非移码突变	254	19.71
	间区	283	23.24

片段	参考	染色体/质粒	起始	终止	长度	基因数	基因编号	基因名	功能
S1	CO92	pMT1质粒	73881	74369	489	1	YPMT1.73	-	磷脂代谢与信号传导
S2	CO92	染色体	2253549	2257250	3702	3	YPO1985、YPO1986、YPO1987	-	糖基化修饰
S3	CO92	染色体	2350433	2352337	1905	1	YPO2071	-	DNA解旋酶DinG样蛋白
S4	CO92	染色体	2370557	2403064	32508	42	YPO2096~YPO2134	tnpA、rzpR、 y1062	噬菌体相关功能
S5	CO92	染色体	2789116	2790121	1006	2	YPO2488、YPO2489	-	DUF2247 家族蛋白
S6	CO92	染色体	1923715	1924944	1230	1	YPO1687	alr	广谱型氨基酸消旋酶
S7	CO92	染色体	2537797	2538729	933	1	YPO2258	araC	AraC 家族转录调控因子
S8	CO92	染色体	3402002	3404908	2907	2	YPO3046、YPO3047	ydeN	硫酸酯酶

Genomic diversity and selection pressure analyses of low-virulence Yersinia pestis lineages

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