Interaction between Selection and Biased Gene Conversion in Mammalian Protein-Coding Sequence Evolution Revealed by a Phylogenetic Covariance Analysis

International audienceAccording to the nearly-neutral model, variation in long-term effective population size among species should result in correlated variation in the ratio of nonsynonymous over synonymous substitution rates (dN/dS). Previous empirical investigations in mammals have been consistent with this prediction, suggesting an important role for nearly-neutral effects on protein-coding sequence evolution. GC-biased gene conversion (gBGC), on the other hand, is increasingly recognized as a major evolutionary force shaping genome nucleotide composition. When sufficiently strong compared with random drift, gBGC may significantly interfere with a nearly-neutral regime and impact dN/dS in a complex manner. Here, we investigate the phylogenetic correlations between dN/dS, the equilibrium GC composition (GC*), and several life-history and karyotypic traits in placental mammals. We show that the equilibrium GC composition decreases with body mass and increases with the number of chromosomes, suggesting a modulation of the strength of biased gene conversion due to changes in effective population size and genome-wide recombination rate. The variation in dN/dS is complex and only partially fits the prediction of the nearly-neutral theory. However, specifically restricting estimation of the dN/dS ratio on GC-conservative transversions, which are immune from gBGC, results in correlations that are more compatible with a nearly-neutral interpretation. Our investigation indicates the presence of complex interactions between selection and biased gene conversion and suggests that further mechanistic development is warranted, to tease out mutation, selection, drift, and conversion