Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona, United States of America.
PLoS One. 2007 May 23;2(5):e461. doi: 10.1371/journal.pone.0000461.
Anthrax, caused by the bacterium Bacillus anthracis, is a disease of historical and current importance that is found throughout the world. The basis of its historical transmission is anecdotal and its true global population structure has remained largely cryptic. Seven diverse B. anthracis strains were whole-genome sequenced to identify rare single nucleotide polymorphisms (SNPs), followed by phylogenetic reconstruction of these characters onto an evolutionary model. This analysis identified SNPs that define the major clonal lineages within the species. These SNPs, in concert with 15 variable number tandem repeat (VNTR) markers, were used to subtype a collection of 1,033 B. anthracis isolates from 42 countries to create an extensive genotype data set. These analyses subdivided the isolates into three previously recognized major lineages (A, B, and C), with further subdivision into 12 clonal sub-lineages or sub-groups and, finally, 221 unique MLVA15 genotypes. This rare genomic variation was used to document the evolutionary progression of B. anthracis and to establish global patterns of diversity. Isolates in the A lineage are widely dispersed globally, whereas the B and C lineages occur on more restricted spatial scales. Molecular clock models based upon genome-wide synonymous substitutions indicate there was a massive radiation of the A lineage that occurred in the mid-Holocene (3,064-6,127 ybp). On more recent temporal scales, the global population structure of B. anthracis reflects colonial-era importation of specific genotypes from the Old World into the New World, as well as the repeated industrial importation of diverse genotypes into developed countries via spore-contaminated animal products. These findings indicate humans have played an important role in the evolution of anthrax by increasing the proliferation and dispersal of this now global disease. Finally, the value of global genotypic analysis for investigating bioterrorist-mediated outbreaks of anthrax is demonstrated.
炭疽病是由炭疽杆菌引起的，是一种具有历史和现实重要性的疾病，分布于世界各地。其历史传播的基础是轶事证据，其真实的全球种群结构在很大程度上仍是个谜。对 7 种不同的炭疽杆菌菌株进行全基因组测序，以鉴定罕见的单核苷酸多态性（SNP），然后根据进化模型重建这些特征的系统发育。该分析确定了定义该物种主要克隆谱系的 SNP。这些 SNP 与 15 个可变数串联重复（VNTR）标记一起，用于对来自 42 个国家的 1033 株炭疽杆菌分离株进行亚型分析，创建了一个广泛的基因型数据集。这些分析将分离株分为三个先前公认的主要谱系（A、B 和 C），进一步细分为 12 个克隆亚谱系或亚群，最后分为 221 个独特的 MLVA15 基因型。这种罕见的基因组变异被用于记录炭疽杆菌的进化进程，并建立全球多样性模式。A 谱系的分离株在全球范围内广泛分布，而 B 和 C 谱系则在更有限的空间尺度上出现。基于全基因组同义替换的分子钟模型表明，A 谱系在中全新世（3064-6127 年前）发生了大规模辐射。在更近的时间尺度上，炭疽杆菌的全球种群结构反映了特定基因型从旧世界向新世界的殖民时代传入，以及通过受孢子污染的动物产品向发达国家反复工业传入多种基因型。这些发现表明，人类在炭疽病的进化中发挥了重要作用，通过增加这种现已全球化疾病的增殖和传播来实现。最后，证明了全球基因型分析在调查炭疽生物恐怖主义引发的暴发方面的价值。
