中国主要流行结核分枝杆菌亚谱系在东亚的传播历史
收稿日期: 2025-12-29
修回日期: 2026-03-25
网络出版日期: 2026-04-07
基金资助
国家自然科学基金项目(32470009);深地国家科技重大专项(2024ZD1000602);深地国家科技重大专项(2024ZD1000603);四川大学考古科学中心基金(24SASB01);四川大学考古科学中心基金(24SASB05)
Transmission history of major China-prevalent Mycobacterium tuberculosis sub-lineages in East Asia
Received date: 2025-12-29
Revised date: 2026-03-25
Online published: 2026-04-07
Supported by
National Natural Science Foundation of China(32470009);National Key Science and Technology Special Project for Deep Earth Research(2024ZD1000602);National Key Science and Technology Special Project for Deep Earth Research(2024ZD1000603);Open Research Fund of Center for Archaeological Science, Sichuan University(24SASB01);Open Research Fund of Center for Archaeological Science, Sichuan University(24SASB05)
结核分枝杆菌复合群(Mycobacterium tuberculosis complex，MTBC)在全球广泛传播，引发的结核病对古今人群健康均造成严重威胁。本研究基于中国流行的4个主要MTBC亚谱系(L2.2、L4.2、L4.4和L4.5)的全基因组数据，重建了其在东亚和部分中亚国家的传播和扩张历史。分析结果表明，L2.2以华南为中心建立了密集的传播网络；L4.2体现出中亚-中国西部的跨境传播，L4.4和L4.5表现出东南亚-华南之间的反复传播。种群历史重建的结果表明，各亚谱系经历了15世纪以来的多轮种群扩张以及演化分支数量在近代的快速增长，揭示了MTBC在东亚地区的流行呈现长期历史适应与近现代集中暴发叠加的规律，为中国的区域结核病精准防控提供基因组学证据。
吴畏 , 杨斌 , 周智威 , 原海兵 , 孙群 . 中国主要流行结核分枝杆菌亚谱系在东亚的传播历史[J]. 遗传, 2026 , 48(9) : 921 -930 . DOI: 10.16288/j.yczz.25-345
Mycobacterium tuberculosis complex (MTBC) is distributed globally and has posed a severe threat to human health throughout history. In this study, we analyzed whole-genome data from the four major MTBC sub-lineages prevalent in China (L2.2, L4.2, L4.4, and L4.5) to reconstruct their transmission and expansion histories across East Asia and parts of Central Asia. We found that L2.2 has established a highly connected transmission network centered in Southern China, whereas L4.2 is characterized by cross-border transmission between Central Asia and Western China, and L4.4 and L4.5 exhibit repeated transmission events between Southeast Asia and Southern China. By reconstructing their population histories, we demonstrated that these sub-lineages have experienced multi-stage expansions since the 15th century, accompanied by a recent rapid proliferation of evolutionary clades. These findings reveal that the MTBC epidemic in East Asia may follow a pattern of long-term historical adaptation superimposed with recent concentrated outbreaks, providing potential genomic evidence to inform precise regional tuberculosis control strategies in China.
| [1] | World Health Organization. Global tuberculosis report 2025. Geneva: World Health Organization, 2025. |
| [2] | Liu QY, Ma AJ, Wei LH, Pang Y, Wu BB, Luo T, Zhou Y, Zheng HX, Jiang Q, Gan MY, Zuo TY, Liu M, Yang CG, Jin L, Comas I, Gagneux S, Zhao YL, Pepperell CS, Gao Q. China’s tuberculosis epidemic stems from historical expansion of four strains of Mycobacterium tuberculosis. Nat Ecol Evol, 2018, 2(12): 1982-1992. |
| [3] | Liu Y, Wang BX, Liu ZY, Han Y, Tan YJ, Li XJ, Liu JX, Tan SY, Zhang TY. Progress in resistance mechanisms and diagnosis of non-first line anti-TB drugs. Hereditas (Beijing), 2016, 38(10): 928-939. |
| 刘洋, 王邦兴, 刘志永, 韩轶, 谭耀驹, 李昕洁, 刘健雄, 谭守勇, 张天宇. 非一线抗结核药物耐药机制及耐药性诊断研究进展. 遗传, 2016, 38(10): 928-939. | |
| [4] | Wu W, Liu ZC, Chen HQ, Tang YH, Jiang ZZ, Zhang YY, Zhang AD, Zhou ZW, Marks RS, Zhang F, Yuan HB, Yu Y, Mao KS, Dinnyés A, Rastogi N, Xie JP, Sun Q. Cross-continental transmission and host adaptation of Mycobacterium tuberculosis in China unveiled by population history reconstruction and adaptive evolution signal detection. IMetaOmics, 2025, 2(4): e70052. |
| [5] | Wu BB, Zhu WL, Wang Y, Wang Q, Zhou L, Liu ZW, Bi LJ, Barun M, Kreiswirth BN, Chen L, Chen SH, Wang XM, Wang WB. Genetic composition and evolution of the prevalent Mycobacterium tuberculosis lineages 2 and 4 in the Chinese and Zhejiang Province populations. Cell Biosci, 2021, 11(1): 162. |
| [6] | Zhu CD, Yang TT, Yin JF, Jiang H, Takiff HE, Gao Q, Liu QY, Li WM. The global success of Mycobacterium tuberculosis modern Beijing family is driven by a few recently emerged strains. Microbiol Spectr, 2023, 11(4): e0333922. |
| [7] | Li YF, Yang Y, Kong XL, Song WM, Li YM, Li YY, Fang WW, Yang JY, Men D, Yu CB, Yang GR, Han WG, Liu WY, Yan K, Li HC, Liu Y. Transmission dynamics and phylogeography of Mycobacterium tuberculosis in China based on whole-genome phylogenetic analysis. Int J Infect Dis, 2024, 140: 124-131. |
| [8] | Ashton PM, Cha J, Anscombe C, Thuong NTT, Thwaites GE, Walker TM. Distribution and origins of Mycobacterium tuberculosis L 4 in Southeast Asia. Microb Genom, 2023, 9(2): mgen000955. |
| [9] | Chen SF, Zhou YQ, Chen YR, Gu J. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics, 2018, 34(17): i884-i890. |
| [10] | McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res, 2010, 20(9): 1297-1303. |
| [11] | Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol, 2015, 32(1): 268-274. |
| [12] | Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods, 2017, 14(6): 587-589. |
| [13] | Bouckaert R, Heled J, Kühnert D, Vaughan T, Wu CH, Xie D, Suchard MA, Rambaut A, Drummond AJ. BEAST 2: a software platform for Bayesian evolutionary analysis. PLoS Comput Biol, 2014, 10(4): e1003537. |
| [14] | Bielejec F, Baele G, Vrancken B, Suchard MA, Rambaut A, Lemey P. SpreaD3: interactive visualization of spatiotemporal history and trait evolutionary processes. Mol Biol Evol, 2016, 33(8): 2167-2169. |
| [15] | Stucki D, Brites D, Jeljeli L, Coscolla M, Liu QY, Trauner A, Fenner L, Rutaihwa L, Borrell S, Luo T, Gao Q, Kato-Maeda M, Ballif M, Egger M, Macedo R, Mardassi H, Moreno M, Tudo Vilanova G, Fyfe J, Globan M, Thomas J, Jamieson F, Guthrie JL, Asante-Poku A, Yeboah-Manu D, Wampande E, Ssengooba W, Joloba M, Henry Boom W, Basu I, Bower J, Saraiva M, Vaconcellos SEG, Suffys P, Koch A, Wilkinson R, Gail-Bekker L, Malla B, Ley SD, Beck HP, de Jong BC, Toit K, Sanchez-Padilla E, Bonnet M, Gil-Brusola A, Frank M, Penlap Beng VN, Eisenach K, Alani I, Revathi G, Gehre F, Akter S, Ntoumi F, Stewart- Isherwood L, Ntinginya NE, Rachow A, Hoelscher M, Cirillo DM, Skenders G, Hoffner S, Bakonyte D, Stakenas P, Diel R, Crudu V, Moldovan O, Al-Hajoj S, Otero L, Barletta F, Jane Carter E, Diero L, Supply P, Comas I, Niemann S, Gagneux S. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages. Nat Genet, 2016, 48(12): 1535-1543. |
| [16] | Luo T, Comas I, Luo D, Lu B, Wu J, Wei LH, Yang CG, Liu QY, Gan MY, Sun G, Shen X, Liu FY, Gagneux S, Mei J, Lan RS, Wan KL, Gao Q. Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese. Proc Natl Acad Sci USA, 2015, 112(26): 8136-8141. |
| [17] | Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, Willery E, Blum MGB, Rüsch-Gerdes S, Mokrousov I, Aleksic E, Allix-Béguec C, Antierens A, Augustynowicz- Kopeć E, Ballif M, Barletta F, Beck HP, Barry CE 3rd, Bonnet M, Borroni E, Campos-Herrero I, Cirillo D, Cox H, Crowe S, Crudu V, Diel R, Drobniewski F, Fauville- Dufaux M, Gagneux S, Ghebremichael S, Hanekom M, Hoffner S, Jiao WW, Kalon S, Kohl TA, Kontsevaya I, Lillebæk T, Maeda S, Nikolayevskyy V, Rasmussen M, Rastogi N, Samper S, Sanchez-Padilla E, Savic B, Shamputa IC, Shen A, Sng LH, Stakenas P, Toit K, Varaine F, Vukovic D, Wahl C, Warren R, Supply P, Niemann S, Wirth T. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet, 2015, 47(3): 242-249. |
| [18] | Casali N, Nikolayevskyy V, Balabanova Y, Harris SR, Ignatyeva O, Kontsevaya I, Corander J, Bryant J, Parkhill J, Nejentsev S, Horstmann RD, Brown T, Drobniewski F. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat Genet, 2014, 46(3): 279-286. |
| [19] | Zhang LY, Huang FJ, Xu JQ, Gong Z, Xie JP. Acid-resistant genes in Mycobacterium tuberculosis and the underlying regulatory network. Hereditas (Beijing), 2018, 40(7): 546-560. |
| 张沥元, 黄芙静, 许峻旗, 龚真, 谢建平. 结核分枝杆菌酸抗性基因及其调控网络. 遗传, 2018, 40(7): 546-560. | |
| [20] | Ke H, Fan L. Annual progress of immunotherapy for tuberculosis in 2023. Chinese Journal of Tuberculosis and Respiratory Diseases, 2024, 47(4): 371-375. |
| 柯荟, 范琳. 结核病免疫治疗年度进展2023. 中华结核和呼吸杂志, 2024, 47(4): 371-375. | |
| [21] | Brites D, Gagneux S. Co-evolution of Mycobacterium tuberculosis and Homo sapiens. Immunol Rev, 2015, 264(1): 6-24. |
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:
