A NOVEL SPECTRAL METHOD FOR INFERRING GENERAL DIPLOID SELECTION FROM TIME SERIES GENETIC DATA.
A NOVEL SPECTRAL METHOD FOR INFERRING GENERAL DIPLOID SELECTION FROM TIME SERIES GENETIC DATA.
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DOI：
10.1214/14-aoas764
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Song YS
中科院分区：
文献类型：
--
作者：
Steinrücken M;Bhaskar A;Song YS
来自实验进化研究和古代DNA样本的时间序列遗传变异数据的增加，为鉴定处于选择压力下的基因组区域和估计其相关适应度参数创造了新的机会。然而，考虑到观察到的时间DNA数据，计算群体等位基因频率动态的非中性模型的可能性是一个具有挑战性的问题。在这里，我们开发了一种新的频谱算法来分析和有效地整合连续时间点之间所有可能的频率轨迹。这一进展规避了现有方法的局限性，这些方法需要在数值逼近所需积分时微调种群等位基因频率空间的离散化。此外，我们的方法足够灵活，可以处理一般的二倍体选择模型，其中杂合子和纯合子的适应度参数可以取任意值，而以前的方法只关注少数有限的选择模型。我们证明了我们的方法在模拟数据上的实用性，并将其应用于分析与马的皮毛颜色相关的遗传位点的古代DNA数据。与之前的研究相比，我们对整个适应度参数空间的探索表明，杂合子优势形式的平衡选择可能作用于这些位点。
The increased availability of time series genetic variation data from experimental evolution studies and ancient DNA samples has created new opportunities to identify genomic regions under selective pressure and to estimate their associated fitness parameters. However, it is a challenging problem to compute the likelihood of non-neutral models for the population allele frequency dynamics, given the observed temporal DNA data. Here, we develop a novel spectral algorithm to analytically and efficiently integrate over all possible frequency trajectories between consecutive time points. This advance circumvents the limitations of existing methods which require fine-tuning the discretization of the population allele frequency space when numerically approximating requisite integrals. Furthermore, our method is flexible enough to handle general diploid models of selection where the heterozygote and homozygote fitness parameters can take any values, while previous methods focused on only a few restricted models of selection. We demonstrate the utility of our method on simulated data and also apply it to analyze ancient DNA data from genetic loci associated with coat coloration in horses. In contrast to previous studies, our exploration of the full fitness parameter space reveals that a heterozygote-advantage form of balancing selection may have been acting on these loci.
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