Neutral genomic microevolution of a recently emerged pathogen, Salmonella enterica serovar Agona. Salmonella enterica subsp. enterica serovar Agona str. 63.H.87 isolate:WS1035

Salmonella enterica serovar Agona has caused multiple food-borne outbreaks of gastroenteritis since it was first isolated in 1952. We compared the genomic contents of 73 isolates from global sources, including five distinct outbreaks and sporadic infections. Agona consists of three lineages with minimal mutational diversity: only 846 single nucleotide polymorphisms (SNPs) have accumulated in the non-repetitive, core genome since Agona evolved in 1932 and underwent a major population expansion in the 1960s. Homologous recombination with other serovars of S. enterica imported 42 recombinational tracts (360 kb) in 5/143 nodes within the genealogy, which resulted in 3164 additional SNPs. In contrast to this paucity of genetic diversity, Agona is highly diverse according to pulsed field gel electrophoresis (PFGE), which is used to assign isolates to outbreaks. PFGE diversity reflects a highly dynamic pan-genome associated with the gain or loss (indels) of 51 bacteriophages, 10 plasmids, and 6 integrative conjugational systems (ICE/IMEs). Unlike the core genome, these indels occurred repeatedly in independent nodes (homoplasies), resulting in inaccurate PFGE genealogies. Most of these indels did not affect cargo genes relevant to infection, other than antibiotic resistance, and plasmids and ICE/IMEs were not correlated with homologous recombination. Each outbreak was caused by an independent clade, without outbreak-associated genomic features. Thus, most of the genetic diversity within this recently emerged pathogen reflects changes in the accessory genome, or is due to recombination, but these changes probably reflect neutral processes rather than Darwinian selection.

肠炎沙门氏菌阿贡纳血清型（Salmonella enterica serovar Agona）自1952年首次被分离以来，已引发多起食源性胃肠炎暴发事件。本研究对73株来自全球不同来源的分离株开展基因组内容比较分析，这些分离株涵盖5起明确的暴发事件及散发病例。阿贡纳血清型包含3个进化谱系，其突变多样性极低：自1932年该菌群演化形成并于20世纪60年代发生大规模种群扩张以来，非重复核心基因组仅积累了846个单核苷酸多态性（single nucleotide polymorphisms, SNPs）。在其系统发育谱系的143个节点中，有5个节点发生了与其他肠炎沙门氏菌血清型的同源重组事件，导入了42个重组片段（总长360 kb），由此额外产生了3164个SNPs。与核心基因组极低的遗传多样性形成鲜明对比的是，阿贡纳血清型在脉冲场凝胶电泳（pulsed field gel electrophoresis, PFGE）分型中呈现出高度多样性，而该技术正是用于将分离株归类至不同暴发事件的常规检测手段。PFGE分型所反映的多样性，实则与高度动态的泛基因组密切相关——该泛基因组伴随51个噬菌体、10个质粒以及6个整合接合元件（integrative conjugational systems, ICE/IMEs）的获得或缺失（插入缺失变异，indels）而发生动态变化。与核心基因组不同，这些插入缺失变异在独立的系统发育节点中多次独立发生（即同塑性变异），进而导致基于PFGE构建的系统发育树出现不准确的拓扑结构。上述绝大多数插入缺失变异并未影响噬菌体、质粒及整合接合元件所携带的与感染相关的功能基因，仅抗生素抗性基因除外；且质粒与整合接合元件的携带情况与同源重组事件并无相关性。每一起暴发事件均由独立的进化枝所引发，未携带与暴发相关的特异性基因组特征。综上，这一新近出现的致病菌所具有的大部分遗传多样性，要么源于附属基因组的变异，要么源自同源重组事件，而这些变异过程更可能属于中性演化过程，而非达尔文自然选择作用的结果。