Genomic-epidemiological analysis of 15 million SARS-CoV-2 genomes reveals accelerated fitness gain of JN.1 lineage

Zhong-yi Lei; Qian-tong Jin; Xiao-min Zhang; Xiao-chen Bo; Zi-lin Ren; Yi-gang Tong; Ming Ni

doi:10.1016/j.virs.2026.03.015

April 2026

. doi: 10.1016/j.virs.2026.03.015

Citation: Zhong-yi Lei, Qian-tong Jin, Xiao-min Zhang, Xiao-chen Bo, Zi-lin Ren, Yi-gang Tong, Ming Ni. Genomic-epidemiological analysis of 15 million SARS-CoV-2 genomes reveals accelerated fitness gain of JN.1 lineage .VIROLOGICA SINICA, 2026, 41(2) : 382-391. http://dx.doi.org/10.1016/j.virs.2026.03.015

基于1500万SARS-CoV-2基因组的基因组流行病学分析揭示JN.1谱系适应性增长加速

雷中怡 ^a,b ,
金倩彤 ^c,d ,
张晓敏 ^b ,
伯晓晨 ^b ,
任子林 ^c,d,, ,
童贻刚 ^a,, ,
倪铭 ^b,,

a 北京化工大学生命科学与技术学院, 中国, 北京, 100029;
b 中国人民解放军军事科学院军事医学研究院先进与交叉生物技术研究所, 中国, 北京, 100850;
c 中国农业科学院长春兽医研究所, 病原体与生物安全国家重点实验室, 吉林省人兽共患病防治重点实验室, 中国, 长春, 130122;
d 东北师范大学信息科学与技术学院, 中国, 长春, 130117

通讯作者： 任子林, zilin.ren@outlook.com; 童贻刚, tongyigang@mail.buct.edu.cn; 倪铭, niming@bmi.ac.cn
收稿日期： 2026-01-15
录用日期： 2026-03-30

摘要

SARS-CoV-2自出现以来，在全球范围内引发了多轮传播浪潮，先后经历了Alpha、Delta、早期 Omicron（BA.1—BA.5）、XBB以及近期占主导地位的JN.1等谱系的演替。尽管早期Omicron相较于Delta谱系具有显著适应性优势这一现象已得到广泛认识，但针对2020至2025年间SARS-CoV-2适应性变化的系统评估仍然不足。本文分析了截至2025年5月的1523万余条SARS-CoV-2基因组数据。结果显示，病毒Spike蛋白中突变的累积速度随时间持续加快，而其他病毒蛋白中的这一趋势则逐渐放缓。基于贝叶斯基因组流行病学框架的分析表明，2021至2025年间，病毒谱系适应性总体呈近似线性增长。值得注意的是，JN.1谱系的适应性提升速率显著高于XBB及更早期的Omicron谱系。进一步对JN.1特征突变的分析发现，其受体结合域中的突变相较其他谱系可引起更明显的残基亲疏水性、电荷及结构表面暴露变化。上述结果提示，JN.1可能代表了一个相对独立的进化阶段，并凸显了持续开展基因组监测的重要性。
- SARS-CoV-2进化
- , JN.1谱系
- , 基因组流行病学
- , 谱系适应性
- , 理化和结构性质

Genomic-epidemiological analysis of 15 million SARS-CoV-2 genomes reveals accelerated fitness gain of JN.1 lineage

Zhong-yi Lei ^a,b ,
Qian-tong Jin ^c,d ,
Xiao-min Zhang ^b ,
Xiao-chen Bo ^b ,
Zi-lin Ren ^c,d,, ,
Yi-gang Tong ^a,, ,
Ming Ni ^b,,

a. College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China;
b. Advanced & Interdisciplinary Biotechnology, Academy of Military Medical Sciences, Beijing, 100850, China;
c. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun, 130122, China;
d. School of Information Science and Technology, Northeast Normal University, Changchun, 130117, China

Corresponding author: Zi-lin Ren, zilin.ren@outlook.com Yi-gang Tong, tongyigang@mail.buct.edu.cn Ming Ni, niming@bmi.ac.cn
Received Date: 15 January 2026
Accepted Date: 30 March 2026

Abstract

The evolution of SARS-CoV-2 has been driven by successive globally circulating waves, including the Alpha and Delta lineages, early Omicron (BA.1-BA.5), XBB, and the recently dominant JN.1 lineages. Although the marked advantage in fitness of early Omicron over Delta lineages has been recognized, there is a lack of systematic evaluation of SARS-CoV-2 fitness across 2020 to 2025. Here, we analyzed 15.23 million SARS-CoV-2 genomes available through May 2025. The accumulation of mutations in the spike protein of the virus has continued to accelerate over time, whereas the trend slowed in the other viral proteins. Using a Bayesian genomic-epidemiological framework, we estimated that lineage fitness increased approximately linearly from 2021 to 2025. Notably, JN.1 lineages exhibited a significantly higher rate of fitness gain than their predecessor XBB and earlier Omicron lineages. We further analyzed characteristic mutations of JN.1 and found that those in the receptor-binding domain were associated with larger alterations in residue hydropathy, charge, and structural surface exposure relative to other lineages. These findings suggest JN.1 as a distinct evolutionary stage and underscore the importance of sustained genomic surveillance.
- SARS-CoV-2 evolution
- , JN.1
- , Genomic epidemiology
- , Lineage fitness
- , Physicochemical and structural feature

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