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腾讯登录PNAS：详细绘制出大肠杆菌DNA突变过程图谱
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来自美国印第安纳大学的生物学家和信息学家绘制出一个有机体中迄今为止最为广泛的突变过程图谱之一，这有助于揭示出新的关于突变分子性质方面的进化信息和这些可遗传变化是如何快速发生的。<!--more-->
通过分析模式原核生物大肠杆菌在没有自然选择性压力的情况下经过20万次传代培养时所发生的精确基因组变化，印第安纳大学文理学院生物学系教授Patricia L. Foster和同事们发现大肠杆菌DNA的自发性突变率实际上要比人们之前所认为的低3倍。相关研究结果于近期在线刊登在PNAS期刊上。
这项新的研究也注意到，负责监控新复制的DNA和检测复制错误的错配修复蛋白不仅让突变率保持较低的水平，而且也可能维持基因组中G-C含量和A-T含量之间的平衡。
Foster说，“我们知道即便在没有自然选择的条件下，进化也会进行，这是因为新的突变是在基因组上是被随机地修复的。因此，如果我们想要确定特异性进化变化模式是否是由自然选择促进的，那么了解在没有自然选择下的预期模式也是极其重要的。在这项研究中，我们让自然选择促进或消除大肠杆菌基因组突变的能力最小化，因此我们确定自发性突变的速率和分子图谱，这就允许我们能够捕获基本上所有的但不导致这种细菌死亡的突变。”
在利用错误修复存在缺陷(这会导致突变率增加到100多倍)的大肠杆菌菌株中进行的平行突变积累实验中，研究人员分析了将近2000个突变，结果发现这些突变强烈地导致基因组中的A-T碱基对偏向G-C碱基对，这与正常细菌中观察到的情形相反。
<br/><strong>大肠杆菌染色体</strong><br/>
Foster注意到，“在几乎所有有机体中自发性碱基对替换的分子图谱是由G-C碱基对转变到A-T碱基对所主导的，这就倾向于促进基因组含有较高水平的A-T含量。因为基因组A-T含量存在广泛的变化，所以必定有某种选择性压力或者非适应性机制能够促使基因组含有水平增加的G-C含量。”
在这项研究中，研究人员证实错配修复是决定基因组中发生的突变类型和确定基因组碱基组成的一个主要因素。因为错配修复活性能够被环境所影响，所以这项研究的另一个影响就是突变模式可能用于司法鉴定中以便有助于确定一个特定的细菌菌株来源于何处。(生物谷Bioon.com)
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<img src="http://www.bioon.com/biology/UploadFiles/201209/2012091222444973.gif" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1073/pnas.1210309109" target="_blank">doi: 10.1073/pnas.1210309109</a>
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<br/><strong>Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing</strong><br/>
Heewook Leea, Ellen Popodib, Haixu Tanga, and Patricia L. Foster
Knowledge of the rate and nature of spontaneous mutation is fundamental to understanding evolutionary and molecular processes. In this report, we analyze spontaneous mutations accumulated over thousands of generations by wild-type Escherichia coli and a derivative defective in mismatch repair (MMR), the primary pathway for correcting replication errors. The major conclusions are (i) the mutation rate of a wild-type E. coli strain is ∼1 × 10−3 per genome per generation; (ii) mutations in the wild-type strain have the expected mutational bias for G:C > A:T mutations, but the bias changes to A:T > G:C mutations in the absence of MMR; (iii) during replication, A:T > G:C transitions preferentially occur with A templating the lagging strand and T templating the leading strand, whereas G:C > A:T transitions preferentially occur with C templating the lagging strand and G templating the leading strand; (iv) there is a strong bias for transition mutations to occur at 5′ApC3′/3′TpG5′ sites (where bases 5′A and 3′T are mutated) and, to a lesser extent, at 5′GpC3′/3′CpG5′ sites (where bases 5′G and 3′C are mutated); (v) although the rate of small (≤4 nt) insertions and deletions is high at repeat sequences, these events occur at only 1/10th the genomic rate of base-pair substitutions. MMR activity is genetically regulated, and bacteria isolated from nature often lack MMR capacity, suggesting that modulation of MMR can be adaptive. Thus, comparing results from the wild-type and MMR-defective strains may lead to a deeper understanding of factors that determine mutation rates and spectra, how these factors may differ among organisms, and how they may be shaped by environmental conditions.
<br/>来源：生物谷
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来自美国印第安纳大学的生物学家和信息学家绘制出一个有机体中迄今为止最为广泛的突变过程图谱之一，这有助于揭示出新的关于突变分子性质方面的进化信息和这些可遗传变化是如何快速发生的。<!--more-->
通过分析模式原核生物大肠杆菌在没有自然选择性压力的情况下经过20万次传代培养时所发生的精确基因组变化，印第安纳大学文理学院生物学系教授Patricia L. Foster和同事们发现大肠杆菌DNA的自发性突变率实际上要比人们之前所认为的低3倍。相关研究结果于近期在线刊登在PNAS期刊上。
这项新的研究也注意到，负责监控新复制的DNA和检测复制错误的错配修复蛋白不仅让突变率保持较低的水平，而且也可能维持基因组中G-C含量和A-T含量之间的平衡。
Foster说，“我们知道即便在没有自然选择的条件下，进化也会进行，这是因为新的突变是在基因组上是被随机地修复的。因此，如果我们想要确定特异性进化变化模式是否是由自然选择促进的，那么了解在没有自然选择下的预期模式也是极其重要的。在这项研究中，我们让自然选择促进或消除大肠杆菌基因组突变的能力最小化，因此我们确定自发性突变的速率和分子图谱，这就允许我们能够捕获基本上所有的但不导致这种细菌死亡的突变。”
在利用错误修复存在缺陷(这会导致突变率增加到100多倍)的大肠杆菌菌株中进行的平行突变积累实验中，研究人员分析了将近2000个突变，结果发现这些突变强烈地导致基因组中的A-T碱基对偏向G-C碱基对，这与正常细菌中观察到的情形相反。
<br/><strong>大肠杆菌染色体</strong><br/>
Foster注意到，“在几乎所有有机体中自发性碱基对替换的分子图谱是由G-C碱基对转变到A-T碱基对所主导的，这就倾向于促进基因组含有较高水平的A-T含量。因为基因组A-T含量存在广泛的变化，所以必定有某种选择性压力或者非适应性机制能够促使基因组含有水平增加的G-C含量。”
在这项研究中，研究人员证实错配修复是决定基因组中发生的突变类型和确定基因组碱基组成的一个主要因素。因为错配修复活性能够被环境所影响，所以这项研究的另一个影响就是突变模式可能用于司法鉴定中以便有助于确定一个特定的细菌菌株来源于何处。(生物谷Bioon.com)
<div id="ztload">
<div></div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201209/2012091222444973.gif" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1073/pnas.1210309109" target="_blank">doi: 10.1073/pnas.1210309109</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing</strong><br/>
Heewook Leea, Ellen Popodib, Haixu Tanga, and Patricia L. Foster
Knowledge of the rate and nature of spontaneous mutation is fundamental to understanding evolutionary and molecular processes. In this report, we analyze spontaneous mutations accumulated over thousands of generations by wild-type Escherichia coli and a derivative defective in mismatch repair (MMR), the primary pathway for correcting replication errors. The major conclusions are (i) the mutation rate of a wild-type E. coli strain is ∼1 × 10−3 per genome per generation; (ii) mutations in the wild-type strain have the expected mutational bias for G:C > A:T mutations, but the bias changes to A:T > G:C mutations in the absence of MMR; (iii) during replication, A:T > G:C transitions preferentially occur with A templating the lagging strand and T templating the leading strand, whereas G:C > A:T transitions preferentially occur with C templating the lagging strand and G templating the leading strand; (iv) there is a strong bias for transition mutations to occur at 5′ApC3′/3′TpG5′ sites (where bases 5′A and 3′T are mutated) and, to a lesser extent, at 5′GpC3′/3′CpG5′ sites (where bases 5′G and 3′C are mutated); (v) although the rate of small (≤4 nt) insertions and deletions is high at repeat sequences, these events occur at only 1/10th the genomic rate of base-pair substitutions. MMR activity is genetically regulated, and bacteria isolated from nature often lack MMR capacity, suggesting that modulation of MMR can be adaptive. Thus, comparing results from the wild-type and MMR-defective strains may lead to a deeper understanding of factors that determine mutation rates and spectra, how these factors may differ among organisms, and how they may be shaped by environmental conditions.
<br/>来源：生物谷
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