ESI and CEC, Biosciences, University of Exeter , Penryn Campus, Penryn, Cornwall TR10 9EZ , UK.
Philos Trans R Soc Lond B Biol Sci. 2019 May 13;374(1772):20180094. doi: 10.1098/rstb.2018.0094.
CRISPR-Cas immune systems are present in around half of bacterial genomes. Given the specificity and adaptability of this immune mechanism, it is perhaps surprising that they are not more widespread. Recent insights into the requirement for specific host factors for the function of some CRISPR-Cas subtypes, as well as the negative epistasis between CRISPR-Cas and other host genes, have shed light on potential reasons for the partial distribution of this immune strategy in bacteria. In this study, we examined how mutations in the bacterial mismatch repair system, which are frequently observed in natural and clinical isolates and cause elevated host mutation rates, influence the evolution of CRISPR-Cas-mediated immunity. We found that hosts with a high mutation rate very rarely evolved CRISPR-based immunity to phage compared to wild-type hosts. We explored the reason for this effect and found that the higher frequency at which surface mutants pre-exist in the mutator host background causes them to rapidly become the dominant phenotype under phage infection. These findings suggest that natural variation in bacterial mutation rates may, therefore, influence the distribution of CRISPR-Cas adaptive immune systems. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.
CRISPR-Cas 免疫系统存在于大约一半的细菌基因组中。鉴于这种免疫机制的特异性和适应性，它们的分布并不广泛，这也许令人惊讶。最近对某些 CRISPR-Cas 亚型的功能所需的特定宿主因子的深入了解，以及 CRISPR-Cas 与其他宿主基因之间的负遗传相互作用，揭示了这种免疫策略在细菌中部分分布的潜在原因。在这项研究中，我们研究了细菌错配修复系统的突变（在自然和临床分离物中经常观察到）如何影响 CRISPR-Cas 介导的免疫的进化，该系统导致宿主突变率升高。我们发现，与野生型宿主相比，具有高突变率的宿主很少进化出针对噬菌体的基于 CRISPR 的免疫。我们探讨了这种效应的原因，发现突变体在突变体宿主背景中预先存在的频率更高，导致它们在噬菌体感染下迅速成为主要表型。这些发现表明，细菌突变率的自然变异可能会影响 CRISPR-Cas 适应性免疫系统的分布。本文是关于“原核 CRISPR-Cas 适应性免疫系统的生态学和进化”的讨论专题的一部分。
