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

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

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
Available online: 08 April 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

Electronic Supplementary Material

10.1016j.virs.2026.03.015-ESM.docx
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