An age-of-allele test of neutrality for transposable element insertions.
An age-of-allele test of neutrality for transposable element insertions.
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DOI：
10.1534/genetics.113.158147
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发表时间：
2014-02
期刊：
影响因子：
3.3
通讯作者：
Bergman CM
中科院分区：
文献类型：
--
作者：
Blumenstiel JP;Chen X;He M;Bergman CM
多年来，自然选择如何限制基因组中转座因子（TE）的增殖一直是进化生物学家感兴趣的问题。为了描述人口中的TE动力学，以前的研究使用了换位选择平衡模型，假设一个恒定的换位率。然而，由于已知TE侵入在时间上以突发方式发生，因此这种假设可能不合理。在这里，我们提出了一个测试的中性TE插入，不依赖于一个恒定的换位率的假设。我们认为TE插入的情况下，已确定从一个单一的单倍体参考基因组序列。通过调节个体TE插入等位基因的年龄（通过自插入以来在特定TE序列内发生的独特取代的数量来推断），我们确定在中性下群体样本中插入等位基因频率的概率分布。考虑到不同的人口规模的模型，然后，我们评估我们的模型对等位基因频率数据从190个反转录转座子插入从北美和非洲种群的果蝇样本的预测。使用这个非平衡中性模型，我们能够解释仅基于年龄的TE插入等位基因频率的0.80%的方差。控制的非平衡动力学的换位和主机人口，我们提供的证据，对大多数TE的负选择作用，以及积极的选择作用于TE的一个小子集。我们的工作建立了一个新的框架，用于分析控制大型插入突变（如TE、基因复制或其他拷贝数变异）的进化力量。
How natural selection acts to limit the proliferation of transposable elements (TEs) in genomes has been of interest to evolutionary biologists for many years. To describe TE dynamics in populations, previous studies have used models of transposition–selection equilibrium that assume a constant rate of transposition. However, since TE invasions are known to happen in bursts through time, this assumption may not be reasonable. Here we propose a test of neutrality for TE insertions that does not rely on the assumption of a constant transposition rate. We consider the case of TE insertions that have been ascertained from a single haploid reference genome sequence. By conditioning on the age of an individual TE insertion allele (inferred by the number of unique substitutions that have occurred within the particular TE sequence since insertion), we determine the probability distribution of the insertion allele frequency in a population sample under neutrality. Taking models of varying population size into account, we then evaluate predictions of our model against allele frequency data from 190 retrotransposon insertions sampled from North American and African populations of Drosophila melanogaster. Using this nonequilibrium neutral model, we are able to explain ∼80% of the variance in TE insertion allele frequencies based on age alone. Controlling for both nonequilibrium dynamics of transposition and host demography, we provide evidence for negative selection acting against most TEs as well as for positive selection acting on a small subset of TEs. Our work establishes a new framework for the analysis of the evolutionary forces governing large insertion mutations like TEs, gene duplications, or other copy number variants.