Comparison of the Distribution of Fitness Effects Across Primates.

The distribution of fitness effects (DFE) of mutations is a key determinant of both the efficacy of natural selection and the genetic load of populations. It also provides an indirect summary of the underlying fitness landscape, so the extent to which the DFE is conserved across species is informative about the invariance of those landscapes. Here, we infer the DFE of amino-acid--changing mutations in 38 catarrhine subspecies using site-frequency spectrum (SFS)--based methods. We find that effective population size (Ne) is the dominant axis of cross-species variation in the population-scaled DFE for deleterious mutations, with the apparent clade-level clustering of estimates explained mainly by shared Ne rather than by clade-specific effects. A quantile-based test further shows that the underlying unscaled DFE does not vary significantly across species, so differences are consistent with Ne-rescaling of a single conserved DFE. Consistent with this, the deleterious (non-adaptive) substitution rate ωna declines significantly with Ne, reflecting more efficient purging of slightly deleterious mutations in larger populations. Turning to adaptive substitution, we find weaker, suggestive evidence that the adaptive rate ωa increases with Ne. These conclusions are robust to the choice of DFE parametrization, phylogenetic regression framework, the effect of GC-biased gene conversion, and ancestral misidentification. We also extend the DFE estimation procedure to relax the assumption of additive fitness effects, finding that dominance is only weakly identifiable from the SFS but has minimal impact on comparative DFE inference.