Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Bioessays. 2012 Oct;34(10):885-92. doi: 10.1002/bies.201200050. Epub 2012 Aug 22.
Evolutionary theory assumed that mutations occur constantly, gradually, and randomly over time. This formulation from the "modern synthesis" of the 1930s was embraced decades before molecular understanding of genes or mutations. Since then, our labs and others have elucidated mutation mechanisms activated by stress responses. Stress-induced mutation mechanisms produce mutations, potentially accelerating evolution, specifically when cells are maladapted to their environment, that is, when they are stressed. The mechanisms of stress-induced mutation that are being revealed experimentally in laboratory settings provide compelling models for mutagenesis that propels pathogen-host adaptation, antibiotic resistance, cancer progression and resistance, and perhaps much of evolution generally. We discuss double-strand-break-dependent stress-induced mutation in Escherichia coli. Recent results illustrate how a stress response activates mutagenesis and demonstrate this mechanism's generality and importance to spontaneous mutation. New data also suggest a possible harmony between previous, apparently opposed, models for the molecular mechanism. They additionally strengthen the case for anti-evolvability therapeutics for infectious disease and cancer.
进化理论假设突变会随着时间的推移而不断、逐渐和随机地发生。这种来自 20 世纪 30 年代“现代综合理论”的表述，在分子水平理解基因或突变之前几十年就被人们接受了。从那时起，我们的实验室和其他实验室已经阐明了应激反应激活的突变机制。应激诱导的突变机制会产生突变，可能会加速进化，特别是当细胞不适应环境时，也就是当它们受到压力时。实验中在实验室环境中揭示的应激诱导突变机制为推动病原体-宿主适应、抗生素耐药性、癌症进展和耐药性以及可能的一般进化的突变提供了令人信服的模型。我们讨论了大肠杆菌中依赖双链断裂的应激诱导突变。最近的结果说明了应激反应如何激活突变，并证明了这种机制的普遍性和对自发突变的重要性。新的数据还表明，以前看似对立的分子机制模型之间可能存在某种和谐。它们还进一步支持了针对传染病和癌症的反进化治疗的可能性。
