Comparison of the Distribution of Fitness Effects Across Primates

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ID: 329264
2026
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Abstract
Abstract 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 ( N e ) 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 N e 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 N e -rescaling of a single conserved DFE. Consistent with this, the deleterious (non-adaptive) substitution rate ω na declines significantly with N e , reflecting more efficient purging of slightly deleterious mutations in larger populations. Turning to adaptive substitution, we find weaker, suggestive evidence that the adaptive rate ω a increases with N e . 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. Summary The distribution of fitness effects describes how harmful or beneficial new mutations are and shapes how populations evolve, yet how much it varies between species remains unclear. The authors infer this distribution for protein-coding mutations across 38 primate subspecies from genetic variation. A single underlying distribution, rescaled by each species’ effective population size, accounts for much of the variation: larger populations appear to purge harmful mutations more efficiently and show some evidence of higher adaptive substitution. Relaxing the usual assumption of additive effects, they find that dominance has little impact on the comparative conclusions.
Reference Key
openalex_W7140839050 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Janek Sendrowski, Bjarke Meyer Pedersen, Juraj Bergman, Vasili Pankratov, Thomas Bataillon
Journal current genetics
Year 2026
DOI
10.1093/genetics/iyag252
URL
https://doi.org/10.1093/genetics/iyag252
Keywords Keywords not found

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