Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA.
Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA.
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作者：
Hiroshi Akashi
密码子的使用模式和“沉默”的DNA分歧表明，自然选择之间的同义密码子在果蝇的歧视。在果蝇基因的同义家族中，“优选”密码子始终以较高的频率被发现。这表明了一个简单的沉默DNA进化模型，其中自然选择有利于从非首选密码子到首选密码子的突变（首选变化）。选择相反方向的变化，从优选同义密码子到非优选同义密码子（非优选变化）。在这里，选择同义DNA突变的研究通过比较这两类沉默的DNA变化的进化动力学。外群的序列被用来确定D.黑腹果蝇和拟果蝇的五个基因。群体遗传学理论表明，突变的适应性效应的差异可以从多态性与分歧的比率的比较中推断出来。在D. simulans谱系，证实了沉默位点的选择作用。在28个基因中过量的非偏好固定表明对D.黑腹菌对D.同义突变的选择系数（3.6 <内斯的量级< 1.3）进行了估计。simulans与自然选择的效力降低（内斯< 1的幅度）相一致，D. simulans的有效种群规模小3 - 6倍。黑腹菌同义DNA变化似乎是果蝇中普遍存在的一类弱选择突变。
Patterns of codon usage and "silent" DNA divergence suggest that natural selection discriminates among synonymous codons in Drosophila. "Preferred" codons are consistently found in higher frequencies within their synonymous families in Drosophila melanogaster genes. This suggests a simple model of silent DNA evolution where natural selection favors mutations from unpreferred to preferred codons (preferred changes). Changes in the opposite direction, from preferred to unpreferred synonymous codons (unpreferred changes), are selected against. Here, selection on synonymous DNA mutations is investigated by comparing the evolutionary dynamics of these two categories of silent DNA changes. Sequences from outgroups are used to determine the direction of synonymous DNA changes within and between D. melanogaster and Drosophila simulans for five genes. Population genetics theory shows that differences in the fitness effect of mutations can be inferred from the comparison of ratios of polymorphism to divergence. Unpreferred changes show a significantly higher ratio of polymorphism to divergence than preferred changes in the D. simulans lineage, confirming the action of selection at silent sites. An excess of unpreferred fixations in 28 genes suggests a relaxation of selection on synonymous mutations in D. melanogaster. Estimates of selection coefficients for synonymous mutations (3.6 < magnitude of Nes < 1.3) in D. simulans are consistent with the reduced efficacy of natural selection (magnitude of Nes < 1) in the three- to sixfold smaller effective population size of D. melanogaster. Synonymous DNA changes appear to be a prevalent class of weakly selected mutations in Drosophila.