Sawyer S A, Hartl D L
Department of Mathematics, Washington University, St. Louis, Missouri 63130.
Genetics. 1992 Dec;132(4):1161-76. doi: 10.1093/genetics/132.4.1161.
Frequencies of mutant sites are modeled as a Poisson random field in two species that share a sufficiently recent common ancestor. The selective effect of the new alleles can be favorable, neutral, or detrimental. The model is applied to the sample configurations of nucleotides in the alcohol dehydrogenase gene (Adh) in Drosophila simulans and Drosophila yakuba. Assuming a synonymous mutation rate of 1.5 x 10(-8) per site per year and 10 generations per year, we obtain estimates for the effective population size (N(e) = 6.5 x 10(6)), the species divergence time (tdiv = 3.74 million years), and an average selection coefficient (sigma = 1.53 x 10(-6) per generation for advantageous or mildly detrimental replacements), although it is conceivable that only two of the amino acid replacements were selected and the rest neutral. The analysis, which includes a sampling theory for the independent infinite sites model with selection, also suggests the estimate that the number of amino acids in the enzyme that are susceptible to favorable mutation is in the range 2-23 at any one time. The approach provides a theoretical basis for the use of a 2 x 2 contingency table to compare fixed differences and polymorphic sites with silent sites and amino acid replacements.
在拥有足够近共同祖先的两个物种中，突变位点的频率被建模为泊松随机场。新等位基因的选择效应可以是有利的、中性的或有害的。该模型应用于拟果蝇和雅库布果蝇酒精脱氢酶基因（Adh）中的核苷酸样本构型。假设每年每个位点的同义突变率为1.5×10⁻⁸，每年有10代，我们得到了有效种群大小（Ne = 6.5×10⁶）、物种分化时间（tdiv = 374万年）以及平均选择系数（有利或轻度有害替换的每代σ = 1.53×10⁻⁶）的估计值，尽管可以想象只有两个氨基酸替换是被选择的，其余是中性的。该分析包括带有选择的独立无限位点模型的抽样理论，还表明估计在任何时候该酶中易受有利突变影响的氨基酸数量在2 - 23范围内。该方法为使用2×2列联表比较固定差异、多态性位点与沉默位点以及氨基酸替换提供了理论基础。
