Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila.
Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila.
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作者：
H. Akashi;S. Schaeffer
在大肠杆菌、酿酒酵母菌和黑腹果蝇中，密码子偏倚可能是由于突变压力、遗传漂变和自然选择之间的平衡而维持的。在这种进化模型下，沉默突变可分为两类：增加密码子偏倚的首选突变和相反方向的非首选突变。这种预测可以通过比较同义变化在种群内分离的频谱来检验；自然选择将提高有利突变相对于有害突变的频率。2个拟花龙牙基因的99个等位基因和8个拟花龙牙基因的5个等位基因的偏好突变和非偏好突变的频率分布在预测方向上存在差异。这一结果证实了沉默突变的适合度类别的存在。最大似然估计表明，在沉默位点的选择强度平均而言，在伪拟盲蝽和拟盲蝽中都非常弱（NS值约为1）。从种内序列变化推断进化过程常常受到固定频率分布假设的阻碍。在确定选择行为时可以避免这种假设，在估计选择强度时可以进行测试。
In Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster, codon bias may be maintained by a balance among mutation pressure, genetic drift, and natural selection favoring translationally superior codons. Under such an evolutionary model, silent mutations fall into two fitness categories: preferred mutations that increase codon bias and unpreferred changes in the opposite direction. This prediction can be tested by comparing the frequency spectra of synonymous changes segregating within populations; natural selection will elevate the frequencies of advantageous mutations relative to that of deleterious changes. The frequency distributions of preferred and unpreferred mutations differ in the predicted direction among 99 alleles of two D. pseudoobscura genes and five alleles of eight D. simulans genes. This result confirms the existence of fitness classes of silent mutations. Maximum likelihood estimates suggest that selection intensity at silent sites is, on average, very weak in both D. pseudoobscura and D. simulans (magnitude of NS approximately 1). Inference of evolutionary processes from within-species sequence variation is often hindered by the assumption of a stationary frequency distribution. This assumption can be avoided when identifying the action of selection and tested when estimating selection intensity.