Reconstructing the History of Variation in Effective Population Size along Phylogenies

The nearly neutral theory predicts specific relations between effective population size (N(e)) 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 N(e). Here, we introduce an integrative framework allowing for an explicit reconstruction of the phylogenetic history of N(e), 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 ([Formula: see text]) and divergence (dN/dS) with respect to N(e). 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 [Formula: see text] and dN/dS as a function of N(e) is too large to be compatible with current estimates of the DFE based on site frequency spectra. The reconstructed history of N(e) 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 N(e). As a result of these opposing trends for N(e) and u, variation in π(S) is intermediate, primarily driven by N(e) but substantially influenced by u. Altogether, our integrative framework provides a quantitative assessment of the role of N(e) and u in modulating patterns of genetic variation, while giving a synthetic picture of their history over the clade.