Lind Peter A, Andersson Dan I
Department of Medical Biochemistry and Microbiology, Uppsala University, S-75123 Uppsala, Sweden.
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17878-83. doi: 10.1073/pnas.0804445105. Epub 2008 Nov 10.
A fundamental biological question is what forces shape the guanine plus cytosine (GC) content of genomes. We studied the specificity and rate of different mutational biases in real time in the bacterium Salmonella typhimurium under conditions of strongly reduced selection and in the absence of the major DNA repair systems involved in repairing common spontaneous mutations caused by oxidized and deaminated DNA bases. The mutational spectrum was determined by whole-genome sequencing of two S. typhimurium mutants that were serially passaged for 5,000 generations. Analysis of 943 identified base pair substitutions showed that 91% were GC-to-TA transversions and 7% were GC-to-AT transitions, commonly associated with 8-oxoG- and deamination-induced damages, respectively. Other types of base pair substitutions constituted the remaining 2% of the mutations. With regard to mutational biases, there was a significant increase in C-to-T transitions on the nontranscribed strand, and for highly expressed genes, C/G-to-T mutations were more common than expected; however, no significant mutational bias with regard to leading and lagging strands of replication or chromosome position were found. These results suggest that, based on the experimentally determined mutational rates and specificities, a bacterial genome lacking the relevant DNA repair systems could, as a consequence of these underlying mutational biases, very rapidly reduce its GC content.
一个基本的生物学问题是，是什么力量塑造了基因组中鸟嘌呤加胞嘧啶（GC）的含量。我们在选择压力大幅降低且缺乏参与修复由氧化和脱氨DNA碱基引起的常见自发突变的主要DNA修复系统的条件下，实时研究了鼠伤寒沙门氏菌中不同突变偏向的特异性和速率。通过对两个连续传代5000代的鼠伤寒沙门氏菌突变体进行全基因组测序来确定突变谱。对943个已鉴定的碱基对替换的分析表明，91%是GC到TA的颠换，7%是GC到AT的转换，分别通常与8-氧代鸟嘌呤和脱氨诱导的损伤相关。其他类型的碱基对替换占突变的其余2%。关于突变偏向，非转录链上C到T的转换显著增加，对于高表达基因，C/G到T的突变比预期更常见；然而，在复制的前导链和后随链或染色体位置方面未发现显著的突变偏向。这些结果表明，根据实验确定的突变率和特异性，由于这些潜在的突变偏向，缺乏相关DNA修复系统的细菌基因组可能会非常迅速地降低其GC含量。
