正如在癌症中观察到的那样，个体诱变剂和 DNA 修复缺陷会产生独特的突变特征，这些特征结合起来在细胞内形成特定的谱。我们推断，类似的过程必定发生在细菌谱系中，这可能允许分解分析来检测 DNA 修复过程的破坏和特定环境诱变剂的暴露。在这里，我们重建了来自 31 个不同细菌物种的 84 个进化枝的突变谱，并发现了不同的突变模式。我们使用超变谱系提取由特定 DNA 修复缺陷驱动的特征，并进一步将光谱解卷积为在不同进化枝内运行的多个特征。我们证明这些特征可以通过细菌系统发育和复制生态位来解释。通过比较来自不同环境和生物位置的进化枝的突变谱，我们识别了与生态位相关的突变特征，然后利用这些特征来推断以前模糊的几个进化枝的主要复制生态位。我们的结果表明，当诱变剂暴露不同时，突变谱可能与细菌复制位点相关，并且可以在这些情况下用于推断已建立和新出现的人类细菌病原体的传播途径。© 2023。作者。

As observed in cancers, individual mutagens and defects in DNA repair create distinctive mutational signatures that combine to form context-specific spectra within cells. We reasoned that similar processes must occur in bacterial lineages, potentially allowing decomposition analysis to detect both disruption of DNA repair processes and exposure to niche-specific mutagens. Here we reconstruct mutational spectra for 84 clades from 31 diverse bacterial species and find distinct mutational patterns. We extract signatures driven by specific DNA repair defects using hypermutator lineages, and further deconvolute the spectra into multiple signatures operating within different clades. We show that these signatures are explained by both bacterial phylogeny and replication niche. By comparing mutational spectra of clades from different environmental and biological locations, we identify niche-associated mutational signatures, and then employ these signatures to infer the predominant replication niches for several clades where this was previously obscure. Our results show that mutational spectra may be associated with sites of bacterial replication when mutagen exposures differ, and can be used in these cases to infer transmission routes for established and emergent human bacterial pathogens.© 2023. The Author(s).