Neisseria meningitidis (the meningococcus) is a major human pathogen with a history of high invasive disease burden, particularly in sub-Saharan Africa. Our current understanding of the evolution of meningococcal genomes is limited by the rarity of large-scale genomic population studies and lack of in-depth investigation of the genomic events associated with routine pathogen transmission. Here, we fill this knowledge gap by a detailed analysis of 2839 meningococcal genomes obtained through a carriage study of over 50,000 samples collected systematically in Burkina Faso, West Africa, before, during, and after the serogroup A vaccine rollout, 2009–2012. Our findings indicate that the meningococcal genome is highly dynamic, with highly recombinant loci and frequent gene sharing across deeply separated lineages in a structured population. Furthermore, our findings illustrate how population structure can correlate with genome flexibility, as some lineages in Burkina Faso are orders of magnitude more recombinant than others. We also examine the effect of selection on the population, in particular how it is correlated with recombination. We find that recombination principally acts to prevent the accumulation of deleterious mutations, although we do also find an example of recombination acting to speed the adaptation of a gene. In general, we show the importance of recombination in the evolution of a geographically expansive population with deep population structure in a short timescale. This has important consequences for our ability to both foresee the outcomes of vaccination programs and, using surveillance data, predict when lineages of the meningococcus are likely to become a public health concern.

中文翻译：

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重组对脑膜炎奈瑟菌种群进化的影响


脑膜炎奈瑟菌（脑膜炎球菌）是一种主要的人类病原体，具有高侵袭性疾病负担的历史，特别是在撒哈拉以南非洲地区。我们目前对脑膜炎球菌基因组进化的理解受到大规模基因组群体研究的罕见性以及缺乏对与常规病原体传播相关的基因组事件的深入研究的限制。在这里，我们通过对 2839 个脑膜炎球菌基因组的详细分析来填补这一知识空白，这些基因组是通过对 2009 年至 2012 年 A 群疫苗推出之前、期间和之后在西非布基纳法索系统收集的 50,000 多个样本进行携带研究而获得的。我们的研究结果表明，脑膜炎球菌基因组是高度动态的，在结构化群体中具有高度重组的基因座和在深度分离的谱系之间频繁的基因共享。此外，我们的研究结果说明了种群结构如何与基因组灵活性相关，因为布基纳法索的一些谱系比其他谱系的重组程度高出几个数量级。我们还研究了选择对群体的影响，特别是它与重组的关系。我们发现重组主要起到防止有害突变积累的作用，尽管我们也发现了重组作用加速基因适应的例子。总的来说，我们展示了重组在短时间内具有深层种群结构的地理广阔种群的进化中的重要性。这对于我们预测疫苗接种计划的结果以及利用监测数据预测脑膜炎球菌谱系何时可能成为公共卫生问题的能力具有重要影响。