The nearly-neutral theory predicts specific relations between effective population size (Ne) and patterns of divergence and polymorphism, which depend on the shape of the distribution of fitness effects (DFE) of new mutations. However, testing these relations is not straightforward, owing to the difficulty in estimating Ne. Here, we introduce an integrative framework allowing for an explicit reconstruction of the phylogenetic history of Ne, thus leading to a quantitative test of the nearly-neutral theory and an estimation of the allometric scaling of the ratios of non-synonymous over synonymous polymorphism (piN/piS) and divergence (dN/dS) with respect to Ne. As an illustration, we applied our method to primates, for which the nearly-neutral predictions were mostly verified. Under a purely nearly-neutral model with a constant DFE across species, we find that the variation in piN/piS and dN/dS as a function of Ne is too large to be compatible with current estimates of the DFE based on site frequency spectra. The reconstructed history of Ne shows a ten-fold variation across primates. The mutation rate per generation u, also reconstructed over the tree by the method, varies over a three-fold range and is negatively correlated with Ne. As a result of these opposing trends for Ne and u, variation in piS is intermediate, primarily driven by Ne but substantially influenced by u. Altogether, our integrative framework provides a quantitative assessment of the role of Ne and u in modulating patterns of genetic variation, while giving a synthetic picture of their history over the clade.

中文翻译：

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重建沿系统发育的有效种群大小的变异历史。

近中性理论预测有效种群大小 (Ne) 与分歧和多态性模式之间的特定关系，这取决于新突变的适应度效应 (DFE) 分布的形状。然而，由于估计 Ne 的困难，测试这些关系并不简单。在这里，我们引入了一个综合框架，允许对 Ne 的系统发育历史进行明确的重建，从而导致对近中性理论的定量测试和对非同义多态性与同义多态性（piN /piS) 和散度 (dN/dS) 相对于 Ne。作为说明，我们将我们的方法应用于灵长类动物，其中几乎中性的预测大多得到验证。在跨物种具有恒定 DFE 的纯近中性模型下，我们发现作为 Ne 函数的 piN/piS 和 dN/dS 的变化太大，无法与当前基于站点频谱的 DFE 估计兼容。Ne 的重建历史显示出灵长类动物的 10 倍变异。每代 u 的突变率也通过该方法在树上重建，在三倍范围内变化，并且与 Ne 负相关。由于 Ne 和 u 的这些相反趋势，piS 的变化是中间的，主要由 Ne 驱动，但受 u 的影响很大。总而言之，我们的综合框架提供了对 Ne 和 u 在调节遗传变异模式中的作用的定量评估，同时给出了它们在整个进化枝上的历史的综合图。