Rates Of Spontaneous Mutation

自发突变率

• 批准号: 8336581
• 负责人: JOHN W. DRAKE
• 金额: $ 89.87万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336581
• 关键词: Affect; Animals; Archaea; Bacteria; Bacteriophage T4; Bacteriophages; Biological Models; Characteristics; Cytolysis; DNA; Escherichia coli; Eubacterium; Evolution; Genes; Genome; Genomics; Human; Individual; Induced Mutation; Maps; Measures; Microbe; Modeling; Mutation; Organism; Pattern; Polyploidy; Process; RNA Phages; Reporter; Reporting; Resolution; Route; Students; System; Testing; Thermus; Thermus thermophilus; Work; base; extreme thermophile; interest; mutant; pathogen

1. Because we often use the rI gene of bacteriophage T4 as a mutation reporter, we sequenced a set of rI-like mutations that did not map at the classical rI locus in order to determine where they did map. Some occupied the gene upstream from rI, or fell in the rIII, rIV or rV genes, but not elsewhere. Because the r genes are involved in lysis inhibition, a classical system of interest to students of evolution, this result resolves ambiguities about how many genes are involved, and also happens to reveal some anomalies in the mutational propensities of those genes. 2. Mutation rates are difficult to measure in riboviruses, the largest class of human pathogens. In particular, the question of whether riboviruses share a common genomic mutation rate has resisted resolution. After many efforts, we have recently established a model system using the phage Q growing on the bacterium Escherichia coli. As expected from a ribovirus, mutation rates are very high, about 0.04 per genome replication. The ratios of different kinds of mutations are somewhat different from those seen in most other organisms, with a particularly high ratio of transition to transversion base substitutions and with very few indels also showing an apparent bias towards single-base insertions. We were also able to test the hypothesis that riboviruses replication by a stamping-machine process rather than by exponential replication, with the stamping-machine hypothesis supported. 3. We reported previously on rates and kinds of mutations in the extreme thermophile Thermus thermophilus. Recently, a report appeared suggesting that this bacterium carries 4-5 copies of its genome, which could have affected our estimates. We have now completed an analysis of this situation which describes ways to calculate mutation rates in the presence of polyploidy, selection, and other distortions, and have concluded that our estimate of the Thermus mutation rate was not significantly affected.

1. 因为我们经常使用噬菌体 T4 的 rI 基因作为突变报告基因，所以我们对一组未映射到经典 rI 位点的 rI 样突变进行了测序，以确定它们映射的位置。有些占据了rI上游的基因，或者落入了rIII、rIV或rV基因，但不在其他地方。由于 r 基因参与裂解抑制，这是进化论学生感兴趣的经典系统，因此这一结果解决了有关有多少基因参与的模糊性，并且也恰好揭示了这些基因突变倾向的一些异常。 2. 人类病原体最大的一类核糖病毒的突变率很难测量。特别是，核糖病毒是否具有共同的基因组突变率的问题一直难以解决。经过多次努力，我们最近建立了一个利用在大肠杆菌上生长的噬菌体Q的模型系统。正如核糖病毒所预期的那样，突变率非常高，每个基因组复制约 0.04 个。不同种类突变的比例与大多数其他生物体中所见的比例有所不同，转换碱基替换的比例特别高，并且很少的插入缺失也表现出明显的单碱基插入偏向。我们还能够测试核糖病毒通过冲压机过程而不是指数复制进行复制的假设，并支持冲压机假设。 3. 我们之前报道过极端嗜热菌的突变率和种类。最近，一份报告表明这种细菌携带 4-5 个基因组拷贝，这可能会影响我们的估计。我们现在已经完成了对这种情况的分析，描述了在多倍体、选择和其他扭曲存在的情况下计算突变率的方法，并得出结论，我们对栖热菌突变率的估计没有受到显着影响。