Neutral genomic microevolution of a recently emerged pathogen, Salmonella enterica serovar Agona. Salmonella enterica subsp. enterica serovar Agona str. 72.A.52 isolate:WS0243

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.

肠炎沙门氏菌阿戈纳血清型（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疫情。本研究对73株全球来源的分离株开展了基因组组成比较分析，这些分离株涵盖5次明确的暴发疫情及散发病例。阿戈纳血清型可划分为三个谱系，其突变多样性极低：自1932年阿戈纳血清型演化形成并于20世纪60年代经历大规模种群扩张以来，其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）。在该菌的系统发育谱系树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，共导入42个重组区段（360 kb），由此额外产生3164个SNPs。与这种极低的遗传多样性形成鲜明反差的是，脉冲场凝胶电泳（pulsed field gel electrophoresis, PFGE）检测结果显示阿戈纳血清型具有高度多样性，该方法常被用于将分离株归类至对应暴发疫情。PFGE多样性反映了高度动态的泛基因组（pan-genome），该泛基因组伴随51个噬菌体、10个质粒以及6个整合接合系统（integrative conjugational systems, ICE/IMEs）的获得与丢失（插入缺失变异，insertions-deletions, indels）。与核心基因组不同，此类插入缺失变异在独立谱系节点中反复出现（同塑性变异（homoplasies）），进而导致PFGE系统发育谱系树的构建结果失真。除抗生素耐药性相关基因外，绝大多数此类插入缺失变异并未影响与感染相关的功能基因；同时，质粒与整合接合系统也未与同源重组存在关联。每一次暴发疫情均由独立的进化枝引发，未携带与暴发相关的基因组特征。综上，这一新近出现的病原菌所具备的绝大多数遗传多样性，要么源于附属基因组（accessory genome）的变异，要么由同源重组导致；但这类变异更可能反映中性进化过程，而非达尔文选择（Darwinian selection）作用。