Long Hongan, Kucukyildirim Sibel, Sung Way, Williams Emily, Lee Heewook, Ackerman Matthew, Doak Thomas G, Tang Haixu, Lynch Michael
Department of Biology, Indiana University, Bloomington
Department of Biology, Hacettepe University, Ankara, Turkey.
Mol Biol Evol. 2015 Sep;32(9):2383-92. doi: 10.1093/molbev/msv119. Epub 2015 May 14.
Deinococcus bacteria are extremely resistant to radiation, oxidation, and desiccation. Resilience to these factors has been suggested to be due to enhanced damage prevention and repair mechanisms, as well as highly efficient antioxidant protection systems. Here, using mutation-accumulation experiments, we find that the GC-rich Deinococcus radiodurans has an overall background genomic mutation rate similar to that of E. coli, but differs in mutation spectrum, with the A/T to G/C mutation rate (based on a total count of 88 A:T → G:C transitions and 82 A:T → C:G transversions) per site per generation higher than that in the other direction (based on a total count of 157 G:C → A:T transitions and 33 G:C → T:A transversions). We propose that this unique spectrum is shaped mainly by the abundant uracil DNA glycosylases reducing G:C → A:T transitions, adenine methylation elevating A:T → C:G transversions, and absence of cytosine methylation decreasing G:C → A:T transitions. As opposed to the greater than 100× elevation of the mutation rate in MMR(-) (DNA Mismatch Repair deficient) strains of most other organisms, MMR(-) D. radiodurans only exhibits a 4-fold elevation, raising the possibility that other DNA repair mechanisms compensate for a relatively low-efficiency DNA MMR pathway. As D. radiodurans has plentiful insertion sequence (IS) elements in the genome and the activities of IS elements are rarely directly explored, we also estimated the insertion (transposition) rate of the IS elements to be 2.50 × 10(-3) per genome per generation in the wild-type strain; knocking out MMR did not elevate the IS element insertion rate in this organism.
嗜放射菌对辐射、氧化和干燥具有极强的抵抗力。据推测,对这些因素的耐受性增强归因于损伤预防和修复机制的强化,以及高效的抗氧化保护系统。在此,我们通过突变积累实验发现,富含鸟嘌呤-胞嘧啶(GC)的耐辐射奇异球菌的总体背景基因组突变率与大肠杆菌相似,但突变谱有所不同,每代每个位点的A/T到G/C突变率(基于88个A:T→G:C转换和82个A:T→C:G颠换的总数)高于另一个方向(基于157个G:C→A:T转换和33个G:C→T:A颠换的总数)。我们提出,这种独特的突变谱主要是由丰富的尿嘧啶DNA糖基化酶减少G:C→A:T转换、腺嘌呤甲基化增加A:T→C:G颠换以及胞嘧啶甲基化缺失减少G:C→A:T转换所形成的。与大多数其他生物体的错配修复(MMR)缺陷(DNA错配修复缺陷)菌株中突变率提高100倍以上不同,MMR缺陷的耐辐射奇异球菌仅表现出4倍的升高,这增加了其他DNA修复机制补偿相对低效的DNA错配修复途径的可能性。由于耐辐射奇异球菌的基因组中有大量插入序列(IS)元件,且很少直接探究IS元件的活性,我们还估计野生型菌株中IS元件的插入(转座)率为每代每个基因组2.50×10⁻³;敲除错配修复并未提高该生物体中IS元件的插入率。