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 nonsynonymous over synonymous polymorphism (πN/πS) 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 πN/πS 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 10-fold variation across primates. The mutation rate per generation u, also reconstructed over the tree by the method, varies over a 3-fold range and is negatively correlated with Ne. As a result of these opposing trends for Ne and u, variation in πS 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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重建有效种群规模沿系统发育变化的历史

近乎中性的理论预测了有效种群大小 (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，由于难以估计 Ne，测试这些关系并不简单。在这里，我们引入了一个综合框架，允许明确重建 Ne 的系统发育历史，从而导致对近乎中性理论的定量检验和非同义多态性与同义多态性 (πN/πS) 比率的异速生长比例估计和相对于 Ne 的散度 (dN/dS)。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。在具有恒定 DFE 跨物种的纯近中性模型下，我们发现，作为 Ne 函数的 πN/πS 和 dN/dS 的变化太大，无法与当前基于站点频谱的 DFE 估计值兼容。Ne 的重建历史显示灵长类动物有 10 倍的变异。同样通过该方法在树上重建的每代突变率 u 在 3 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，πS 的变化是中间的，主要由 Ne 驱动，但在很大程度上受 u 影响。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，同时给出了它们在进化枝上的历史的合成图。