Fitness is strongly influenced by rare mutations of large effect in a microbial mutation accumulation experiment.
Fitness is strongly influenced by rare mutations of large effect in a microbial mutation accumulation experiment.
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DOI：
10.1534/genetics.114.163147
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发表时间：
2014-07
期刊：
影响因子：
3.3
通讯作者：
MacLean RC
中科院分区：
文献类型：
--
作者：
Heilbron K;Toll-Riera M;Kojadinovic M;MacLean RC
我们对突变的进化后果的理解在很大程度上依赖于对突变积累（MA）实验产生的自发突变的速率和适应度效应的估计。我们进行了一个经典的MA实验，在该实验中，频繁采样的MA系与全基因组重测序相结合，以开发一个高突变的铜绿假单胞菌菌株（ΔmutS）的自发突变效应的高分辨率图像。经过644代的突变积累，MA系平均积累了118个突变，我们发现所有系的平均适应度随着时间的推移呈线性衰减。对单个品系适应度变化动态的详细分析表明，适应度总体衰减的很大一部分（42.3%）可归因于罕见的、高度有害的突变的固定（仅占固定突变的0.5%）。此外，我们发现至少0.64%的突变是有益的，并且可能由于正选择而固定。大多数固定突变（82.4%）是碱基替换，我们没有发现非同义突变或基因间突变的选择特征。短索引在固定突变中所占的比例要小得多（17.4%），但我们发现了对编码区引起移码突变的索引的强选择的证据。这些结果有助于量化微生物MA实验中存在的自然选择的数量，并证明适应度的变化受到大效应的罕见突变的强烈影响。
Our understanding of the evolutionary consequences of mutation relies heavily on estimates of the rate and fitness effect of spontaneous mutations generated by mutation accumulation (MA) experiments. We performed a classic MA experiment in which frequent sampling of MA lines was combined with whole genome resequencing to develop a high-resolution picture of the effect of spontaneous mutations in a hypermutator (ΔmutS) strain of the bacterium Pseudomonas aeruginosa. After ∼644 generations of mutation accumulation, MA lines had accumulated an average of 118 mutations, and we found that average fitness across all lines decayed linearly over time. Detailed analyses of the dynamics of fitness change in individual lines revealed that a large fraction of the total decay in fitness (42.3%) was attributable to the fixation of rare, highly deleterious mutations (comprising only 0.5% of fixed mutations). Furthermore, we found that at least 0.64% of mutations were beneficial and probably fixed due to positive selection. The majority of mutations that fixed (82.4%) were base substitutions and we failed to find any signatures of selection on nonsynonymous or intergenic mutations. Short indels made up a much smaller fraction of the mutations that were fixed (17.4%), but we found evidence of strong selection against indels that caused frameshift mutations in coding regions. These results help to quantify the amount of natural selection present in microbial MA experiments and demonstrate that changes in fitness are strongly influenced by rare mutations of large effect.
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影响因子：
3.7
作者：
Jerome JP;Bell JA;Plovanich-Jones AE;Barrick JE;Brown CT;Mansfield LS
通讯作者：
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DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
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Barillot E
DOI：
10.1080/09553005914550241
发表时间：
1959-01-01
期刊：
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY AND RELATED STUDIES IN PHYSICS CHEMISTRY AND MEDICINE
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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