Simulating genealogies of selected alleles in a population of variable size
Simulating genealogies of selected alleles in a population of variable size
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DOI：
10.1017/s0016672301005183
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发表时间：
2001-08-01
影响因子：
1.5
通讯作者：
Slatkin, M
中科院分区：
文献类型：
--
作者：
Slatkin, M
提出了一种重要抽样方法，可以模拟可变大小群体中选定等位基因的历史。通过从当前频率向后模拟直到等位基因丢失，可以生成描述等位基因作为单个突变体产生的拷贝数的样本路径。然后，通过对重复模拟取平均值来估计数量或统计量的数学期望，根据其在马尔可夫链下向前和向后过程的概率比率对每个重复进行加权。该方法用于在指数增长的种群中找到选定等位基因的平均年龄。就对平均等位基因年龄的影响而言，有利于等位基因的选择并不等同于指数增长。为了产生所选等位基因拷贝样本的基因谱系，对只包含所选等位基因的亚群模拟中性聚结模型。根据所得到的等位基因内谱系，可以计算出选择强度的可能性，作为与所选等位基因密切相关的标记位点上观察到的变异水平的函数。该方法用于估计影响欧洲人CCR5位点Delta 32等位基因的选择强度，以及芬兰人群中与结直肠癌相关的MLH1位点突变。
An importance-sampling method is presented that allows the simulation of the history of a selected allele in a population of variable size. A sample path describing the number of copies of an allele that arose as a single mutant is generated by simulating backwards from the current frequency until the allele is lost. The mathematical expectation of a quantity or statistic is then estimated by taking averages over replicate simulations, weighting each replicate by the ratio of its probabilities under the Markov chains for the forward and backwards processes. This method was used to find the average age of a selected allele in an exponentially growing population. In terms of the effect on average allele age, selection in favour of an allele is not equivalent to exponential growth. To generate gene genealogies of a sample of copies of a selected allele, the neutral coalescent model is simulated for the subpopulation containing only the selected allele. From the resulting intra-allelic genealogy, it is possible to calculate the likelihood of the selection intensity as a function of the observed level of variability at marker loci closely linked to the selected allele. This method was used to estimate the intensity of selection affecting the Delta 32 allele at the CCR5 locus in Europeans and a mutant at the MLH1 locus associated with colorectal cancer in the Finnish population.