Table_3_Global Distribution and Evolution of Mycobacterium bovis Lineages.XLSX

Mycobacterium bovis is the main causative agent of zoonotic tuberculosis in humans and frequently devastates livestock and wildlife worldwide. Previous studies suggested the existence of genetic groups of M. bovis strains based on limited DNA markers (a.k.a. clonal complexes), and the evolution and ecology of this pathogen has been only marginally explored at the global level. We have screened over 2,600 publicly available M. bovis genomes and newly sequenced four wildlife M. bovis strains, gathering 1,969 genomes from 23 countries and at least 24 host species, including humans, to complete a phylogenomic analyses. We propose the existence of four distinct global lineages of M. bovis (Lb1, Lb2, Lb3, and Lb4) underlying the current disease distribution. These lineages are not fully represented by clonal complexes and are dispersed based on geographic location rather than host species. Our data divergence analysis agreed with previous studies reporting independent archeological data of ancient M. bovis (South Siberian infected skeletons at ∼2,000 years before present) and indicates that extant M. bovis originated between 715 and 3,556 years BP, with later emergence in the New World and Oceania, likely influenced by trades among countries.

牛分枝杆菌（Mycobacterium bovis）是引发人类人畜共患结核病（zoonotic tuberculosis）的主要致病菌，且在全球范围内常给家畜与野生动物种群带来毁灭性破坏。既往研究基于有限DNA标记（亦称克隆复合体（clonal complexes））提出牛分枝杆菌菌株存在遗传类群的假说，但该病原体的演化与生态特征在全球尺度上的探索仍十分有限。本研究筛选了2600余份公开可用的牛分枝杆菌基因组，并新测序了4株野生动物来源的牛分枝杆菌菌株，最终收集了来自23个国家、涵盖至少24种宿主（包括人类）的1969株基因组，完成了系统发育基因组学（phylogenomics）分析。本研究提出牛分枝杆菌存在4个独立的全球谱系（Lb1、Lb2、Lb3及Lb4），这些谱系可解释当前的疾病分布格局；现有克隆复合体并未完全涵盖这些谱系，且谱系的分布主要以地理区域为划分依据，而非宿主物种。本研究的基因组分歧分析结果与既往报道的古代牛分枝杆菌考古学独立证据（约2000年前的南西伯利亚感染骨骼样本）相一致，且表明现存牛分枝杆菌的起源时间距今715至3556年；其在新大陆与大洋洲的出现时间相对较晚，这一过程大概率受到各国间贸易活动的影响。