Epistasis between Beneficial Mutations and the Phenotype-to-Fitness Map for a ssDNA Virus
Epistasis between Beneficial Mutations and the Phenotype-to-Fitness Map for a ssDNA Virus
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DOI：
10.1371/journal.pgen.1002075
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发表时间：
2011-06-01
期刊：
影响因子：
4.5
通讯作者：
Wichman, Holly A.
中科院分区：
文献类型：
--
作者：
Rokyta, Darin R.;Joyce, Paul;Wichman, Holly A.
基因和个体突变之间的上位性相互作用是遗传系统进化特性的主要决定因素，因此已经有很好的文献记载，但很少有关于有益突变之间上位性相互作用的定量数据，可能是因为这种突变比有害突变罕见得多。我们通过构建具有先前已被鉴定为对ssDNA噬菌体ID 11有益的突变对的基因型，并通过测量这些突变单独和组合的影响，来探索有益突变的上位性。我们构建了36个可能的双突变体中的18个，用于9个可用的有益突变。我们发现，有益突变之间的上位相互作用都是拮抗性的，双突变的影响小于其组成部分单突变的影响之和。我们发现了一些失代偿性相互作用的案例，这是一种极端形式的拮抗上位性，其中第二个突变在第一个突变存在的情况下实际上是有害的。在绝大多数情况下，将两个有益突变合并到同一基因组中的重组不会受到选择的青睐，因为重组体无法竞争其组成的单个突变。为了理解这些结果，我们开发了一个简单的模型，其中突变的表型效应是完全加性的，上位性相互作用是表型-适应性映射形式的结果。我们发现，一个具有中间表型最优和加性表型效应的模型为我们的数据和观察到的上位性相互作用模式提供了一个很好的解释。
Epistatic interactions between genes and individual mutations are major determinants of the evolutionary properties of genetic systems and have therefore been well documented, but few quantitative data exist on epistatic interactions between beneficial mutations, presumably because such mutations are so much rarer than deleterious ones. We explored epistasis for beneficial mutations by constructing genotypes with pairs of mutations that had been previously identified as beneficial to the ssDNA bacteriophage ID11 and by measuring the effects of these mutations alone and in combination. We constructed 18 of the 36 possible double mutants for the nine available beneficial mutations. We found that epistatic interactions between beneficial mutations were all antagonistic-the effects of the double mutations were less than the sums of the effects of their component single mutations. We found a number of cases of decompensatory interactions, an extreme form of antagonistic epistasis in which the second mutation is actually deleterious in the presence of the first. In the vast majority of cases, recombination uniting two beneficial mutations into the same genome would not be favored by selection, as the recombinant could not outcompete its constituent single mutations. In an attempt to understand these results, we developed a simple model in which the phenotypic effects of mutations are completely additive and epistatic interactions arise as a result of the form of the phenotype-to-fitness mapping. We found that a model with an intermediate phenotypic optimum and additive phenotypic effects provided a good explanation for our data and the observed patterns of epistatic interactions.