Experimental estimate of the abundance and effects of nearly neutral mutations in the RNA virus φ6

Experimental estimate of the abundance and effects of nearly neutral mutations in the RNA virus φ6
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DOI:
10.1534/genetics.106.067199
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发表时间:
2007-05-01
期刊:
影响因子:
3.3
通讯作者:
Shen, Haipeng
Shen, Haipeng
中科院分区:
生物学2区
文献类型:
--
作者:
Burch, Christina L.;Guyader, Sebastien;Shen, Haipeng

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虽然中性和近中性突变的频率和影响是至关重要的进化模式和遗传漂变的过程中,这样的突变的小影响,使他们难以研究经验。在这里,我们提出了一个突变积累实验的结果,旨在评估频率的有害突变与不可检测的影响。我们通过使RNA病毒phi 6的独立谱系经受单个个体的重复群体瓶颈来促进自发突变的积累。我们在每个瓶颈之后测量了适应度,以获得具有可检测影响的累积突变的时间和影响的完整信息,并对完整基因组进行测序,以确定适应度测定未检测到的突变数量。为了估计未检测到的突变的影响,我们实施了为数量性状基因座(QTL)数据(OTTO和JONES 2000)开发的似然模型,以根据检测到的突变的测量数量和影响来估计未检测到的突变的数量和影响。使用这种方法,我们估计的U = 0.03的有害突变率和伽马效应的分布与平均值S = 0.093和变异系数= 0.204。虽然我们的U和S的估计属于最近的突变率和真核生物的影响估计的范围内,实验室健身(39%)的可检测到的影响的突变的分数似乎是远远高于在phi 6比真核生物。
Although the frequency and effects of neutral and nearly neutral mutations are critical to evolutionary patterns and processes governed by genetic drift, the small effects of such mutations make them difficult to study empirically Here we present the results of a mutation-accumulation experiment designed to assess the frequencies of deleterious mutations with undetectable effects. We promoted the accumulation of spontaneous mutations by subjecting independent lineages of the RNA virus phi 6 to repeated population bottlenecks of a single individual. We measured fitness following every bottleneck to obtain a complete picture of the timing and effects of the accumulated mutations with detectable effects and sequenced complete genomes to determine the number of mutations that were undetected by the fitness assays. To estimate the effects of the undetected mutations, we implemented a likelihood model developed for quantitative trait locus (QTL) data (OTTO and JONES 2000) to estimate the number and effects of the undetected mutations from the measured number and effects of the detected mutations. Using this method we estimated a deleterious mutation rate of U = 0.03 and a gamma effects distribution with mean s = 0.093 and coefficient of variation = 0.204. Although our estimates of U and s fall within the range of recent mutation rate and effect estimates in eukaryotes, the fraction of mutations with detectable effects on laboratory fitness (39%) appears to be far higher in phi 6 than in eukaryotes.