The properties of spontaneous mutations in the opportunistic pathogen Pseudomonas aeruginosa.
The properties of spontaneous mutations in the opportunistic pathogen Pseudomonas aeruginosa.
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DOI：
10.1186/s12864-015-2244-3
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发表时间：
2016-01-05
期刊：
影响因子：
4.4
通讯作者：
Kassen R
中科院分区：
文献类型：
--
作者：
Dettman JR;Sztepanacz JL;Kassen R
自然的遗传变异最终产生于突变过程。了解进化的原材料是如何产生的，对于充分理解几个基本的进化概念是必要的。我们进行了突变积累实验与野生型和错配修复缺陷，突变株的致病性细菌铜绿假单胞菌，并使用全基因组测序，以揭示全基因组的速率，频谱，分布，领先/落后的偏见，和上下文依赖性的自发突变。野生型碱基对突变率和插入缺失率分别为每代每个核苷酸~10−10和~10−11，错配修复系统的缺陷导致比率增加了两个数量级以上。在野生型株系中观察到对AT的普遍偏向，但在突变株系中逆转为对GC的偏向。在两个复制体中检测到前导链与滞后链复制过程中发生的突变类型的偏倚。突变沿着染色体的分布是非随机的，在复制末端附近和复制起点和末端之间的位置具有峰。在铜绿假单胞菌的自然群体中沿着染色体观察到类似的分布偏倚。位点特异性突变率较高时，焦点核苷酸立即侧翼的C：G配对。突变积累系的全基因组测序允许全面鉴定突变，并揭示了分子和基因组结构的哪些因素影响突变过程。我们的研究提供了一个更完整的观点，即突变、突变修复和偏见的几种机制如何同时产生进化的原材料。本文的在线版本（doi：10.1186/s12864-015-2244-3）包含补充材料，可供授权用户使用。
Natural genetic variation ultimately arises from the process of mutation. Knowledge of how the raw material for evolution is produced is necessary for a full understanding of several fundamental evolutionary concepts. We performed a mutation accumulation experiment with wild-type and mismatch-repair deficient, mutator lines of the pathogenic bacterium Pseudomonas aeruginosa, and used whole-genome sequencing to reveal the genome-wide rate, spectrum, distribution, leading/lagging bias, and context-dependency of spontaneous mutations. Wild-type base-pair mutation and indel rates were ~10−10 and ~10−11 per nucleotide per generation, respectively, and deficiencies in the mismatch-repair system caused rates to increase by over two orders of magnitude. A universal bias towards AT was observed in wild-type lines, but was reversed in mutator lines to a bias towards GC. Biases for which types of mutations occurred during replication of the leading versus lagging strand were detected reciprocally in both replichores. The distribution of mutations along the chromosome was non-random, with peaks near the terminus of replication and at positions intermediate to the replication origin and terminus. A similar distribution bias was observed along the chromosome in natural populations of P. aeruginosa. Site-specific mutation rates were higher when the focal nucleotide was immediately flanked by C:G pairings. Whole-genome sequencing of mutation accumulation lines allowed the comprehensive identification of mutations and revealed what factors of molecular and genomic architecture affect the mutational process. Our study provides a more complete view of how several mechanisms of mutation, mutation repair, and bias act simultaneously to produce the raw material for evolution. The online version of this article (doi:10.1186/s12864-015-2244-3) contains supplementary material, which is available to authorized users.