Reconstructing the History of Variation in Effective Population Size along Phylogenies

The nearly neutral theory predicts specific relations between effective population size (Ne) and patterns of divergence and polymorphism, which depend on the shapeof the distribution of fitness effects (DFE) ofnewmutations. However, testingthese relations is not straight forward, 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(pN=pS) and divergence (dN/dS) withrespect to Ne. As an illustration, we applied our method to primates, for which the nearly neutral predictions were mostly verified. Under a purelynearly neutral model with a constantDFE across species, wefindthat the variationinpN=pS and dN/dS as a functionofNe is too large tobe compatiblewith current estimates of theDFEbased on site frequency spectra. The reconstructed history ofNeshows a 10-fold variation across primates. Themutationratepergenerationu, also reconstructed over thetree by the method, varies over a3-fold range and is negatively correlatedwith Ne. As a result of these opposing trends for Ne and u, variation in pS is intermediate, primarily driven by Ne but substantially influenced byu. Altogether, our integrative framework provides aquantitative assessmentof the role of Ne and u in modulating patterns of genetic variation, while giving a synthetic picture of their history over the clade.

Automated summary

The study introduces an integrative framework for reconstructing the phylogenetic history of Ne, allowing for testing the nearly neutral theory and estimating the evolution of genetic variation patterns. The results show that both Ne and u play important roles in modulating patterns of genetic variation, with opposing trends observed in their variations.