Avoiding dangerous missense: thermophiles display especially low mutation rates.
Avoiding dangerous missense: thermophiles display especially low mutation rates.
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DOI：
10.1371/journal.pgen.1000520
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发表时间：
2009-06
期刊：
影响因子：
4.5
通讯作者：
Drake JW
中科院分区：
文献类型：
--
作者：
Drake JW
在各种基于DNA的微生物，包括病毒、细菌和真核生物的最佳生长条件下，对自发突变率进行了估计。当用基因组突变率表示时，大多数值在0.003-0.004附近，范围不到两倍。由于基因组大小的差异约为104倍，每个平均碱基对的突变率与类似的因素成反比。尽管观察到的基因组速率的共性仍然无法解释，但这意味着非应激微生物的突变率达到了可以通过进化微调的值。一项起源于20世纪20年代、成熟于60年代的见解提出，基因组突变率将反映平均突变的有害影响与进一步降低突变率的成本之间的平衡。如果这一观点是正确的，那么应该通过降低基因组突变率来对抗平均突变的有害影响。人们普遍观察到，许多中性或近中性突变在较高的温度下会变得非常有害，在这种情况下，它们被称为温度敏感型突变。最近，描述了两种微生物嗜热菌，一种细菌和一种古细菌的自发突变的种类和速率。使用一种更新的方法从突变报告基因外推到整个基因组，发现这两种嗜热菌的碱基替换率明显低于中嗜热菌。这一结果首次在实验上支持了在突变的总基因组影响和进一步降低基本突变率的成本之间取得进化平衡的概念。自发突变是进化和疾病的关键驱动因素。在微生物中，大多数突变是有害的，一些是中性的(没有重大影响)，少数是有利的。因为有害突变会降低适合度，所以应该不断地选择能降低自发突变率的抗突变突变。然而，这种削减必然是以一定的代价实现的。因此，突变率应该在进化上收敛于反映这种权衡的值。对于dna微生物来说，观察到的基因组突变率非常(而且神秘地)是不变的，在0.003-0.004之间，范围不到两倍，尽管在具有广泛生活史的生物中，每个平均碱基对的变异很大。增加突变的平均有害影响的环境条件是否可以通过对抗突变基因突变的额外投资来平衡？人们普遍观察到，许多影响轻微的突变在较高的温度下会变得非常有害，因此我们测量了两个嗜热菌，一个细菌和一个考古菌的突变率。值得注意的是，两者的平均突变率都比特征中温值降低了约5倍，其中大部分下降反映了碱基替换率降低了10倍。
Rates of spontaneous mutation have been estimated under optimal growth conditions for a variety of DNA-based microbes, including viruses, bacteria, and eukaryotes. When expressed as genomic mutation rates, most of the values were in the vicinity of 0.003–0.004 with a range of less than two-fold. Because the genome sizes varied by roughly 104-fold, the mutation rates per average base pair varied inversely by a similar factor. Even though the commonality of the observed genomic rates remains unexplained, it implies that mutation rates in unstressed microbes reach values that can be finely tuned by evolution. An insight originating in the 1920s and maturing in the 1960s proposed that the genomic mutation rate would reflect a balance between the deleterious effect of the average mutation and the cost of further reducing the mutation rate. If this view is correct, then increasing the deleterious impact of the average mutation should be countered by reducing the genomic mutation rate. It is a common observation that many neutral or nearly neutral mutations become strongly deleterious at higher temperatures, in which case they are called temperature-sensitive mutations. Recently, the kinds and rates of spontaneous mutations were described for two microbial thermophiles, a bacterium and an archaeon. Using an updated method to extrapolate from mutation-reporter genes to whole genomes reveals that the rate of base substitutions is substantially lower in these two thermophiles than in mesophiles. This result provides the first experimental support for the concept of an evolved balance between the total genomic impact of mutations and the cost of further reducing the basal mutation rate. Spontaneous mutations are key drivers of evolution and disease. In microbes, most mutations are deleterious, some are neutral (without significant impact), and a few are advantageous. Because deleterious mutations reduce fitness, there should be constant selection for antimutator mutations that reduce rates of spontaneous mutation. However, such reductions are necessarily achieved at some cost. Therefore, a mutation rate should converge evolutionarily on a value that reflects this trade-off. For DNA microbes, the observed genomic mutation rate is remarkably (and mysteriously) invariant, in the neighborhood of 0.003–0.004, with a range of less than two-fold despite huge variation per average base pair in organisms with a wide diversity of life histories. Would an environmental condition that increased the average deleterious impact of a mutation be balanced by additional investments in antimutator mutations? It is widely observed that many mutations with mild impacts become strongly deleterious at higher temperatures, so mutation rates were measured in two thermophiles, a bacterium and an archaeon. Remarkably, both displayed average mutation rates reduced by about five-fold from the characteristic mesophilic value, most of the decrease reflecting a 10-fold reduction in the rate of base substitutions.
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影响因子：
3.3
作者：
Mackwan, Reena R.;Carver, Geraldine T.;Grogan, Dennis W.
通讯作者：
Grogan, Dennis W.
DOI：
10.1017/s0016672300010284
发表时间：
1967-01-01
期刊：
GENETICAL RESEARCH
影响因子：
--
作者：
KIMURA, M
通讯作者：
KIMURA, M
DOI：
10.1073/pnas.96.24.13910
发表时间：
1999-11-23
影响因子：
11.1
作者：
Drake, JW;Holland, JJ
通讯作者：
Holland, JJ
影响因子：
3.3
作者：
Schultz, Gary E., Jr.;Drake, John W.
通讯作者：
Drake, John W.
影响因子：
3.3
作者：
Mackwan, Reena R.;Carver, Geraldine T.;Grogan, Dennis W.
通讯作者：
Grogan, Dennis W.