Rates Of Spontaneous Mutation

1.在真细菌嗜热栖热菌中测量自发突变的速率和种类。的突变率和碱基对取代的分数是无法区分的，从以前观察到的古菌酸热硫化叶菌和显着低于其他DNA微生物。这一结果有力地支持了这样的假设，即平均错义突变在较高的温度下更有害，这反过来又驱动了较低的碱基置换速率的进化。这些综合结果也使我们能够重新解释一个经典的研究，得出结论，所有三个领域的生命表现出相同的分子进化速度，但在原核生物中，嗜热生物进化得更慢。 2.我们以前报道过，大多数突变谱包含更多的突变与多个突变比预期的随机分布的突变。烟草花叶病毒中突变的非随机分布被模拟为两个亚群的总和，大多数具有低突变频率，少数具有高突变频率。如果这个结果是普遍的，它将有助于模拟核糖病毒的平均突变率，结合它们在宿主内的快速进化，但随着时间的推移相对基因组稳定性。现在，我们正试图建立一个噬菌体系统，在其中这些问题可以更有效地解决。我们还报道了DNA聚合酶分子在体外复制一个模板可以产生非随机的突变爆发，这表明相当少的聚合酶分子具有突变表型。现在我们正在建立系统来确定这些事件的分子基础。 迄今为止，我们发现的证据表明，至少有一些聚合酶分子既有更大的持续合成能力和降低保真度。

1. Rates and kinds of spontaneous mutations were measured in the eubacterial thermophile Thermus thermophilus. The mutation rate and fraction of base-pair substitutions were indistinguishable from those observed previously in the archaeon Sulfolobus acidocaldarius and were markedly lower than in other DNA microbes. This result strongly supports the hypothesis that the average missense mutation is more deleterious at higher temperatures, which in turn drives the evolution of lower rates of base substitution. These combined results also allow us to reinterpret a classical study to conclude that all three domains of life exhibit the same rate of molecular evolution, but that among the prokaryotes, the thermophiles evolve more slowly. 2. We reported previously that most mutational spectra contain more mutants with multiple mutations than expected from a random distribution of the mutations. The nonrandom distribution of mutations in tobacco mosaic virus has been modeled as the sum of two sub-populations, a majority with a low mutation frequency and a minority with a high mutation frequency. If this result is general, it will help to model the average mutation rate of riboviruses in combination with their rapid evolution within the host but relative genomic stability over time. Now we are attempting to establish a phage system in which such questions can be more efficiently addressed. We also reported that DNA polymerase molecules copying a template in vitro can produce nonrandom bursts of mutations, suggesting that a substantial minority of the polymerase molecules have a mutator phenotype. Now we are establishing systems to determine the molecular basis of such events. To date, we find evidence suggesting that at least some polymerase molecules have both greater processivity and reduced fidelity.