The nearly neutral theory of molecular evolution predicts that small populations should accumulate deleterious mutations at a faster rate than large populations. The analysis of nonsynonymous (d N) versus synonymous (d S) substitution rates in birds versus mammals, however, has provided contradictory results, questioning the generality of the nearly neutral theory. Here we analyzed the impact of life history traits, taken as proxies of the effective population size, on molecular evolutionary and population genetic processes in amniotes, including the so far neglected reptiles. We report a strong effect of species body mass, longevity, and age of sexual maturity on genome-wide patterns of polymorphism and divergence across the major groups of amniotes, in agreement with the nearly neutral theory. Our results indicate that the rate of protein evolution in amniotes is determined in the first place by the efficiency of purifying selection against deleterious mutations-and this is true of both radical and conservative amino acid changes. Interestingly, the among-species distribution of d N /d S in birds did not follow this general trend: d N /d S was not higher in large, long-lived than in small, short-lived species of birds. We show that this unexpected pattern is not due to a more narrow range of life history traits, a lack of correlation between traits and N e , or a peculiar distribution of fitness effects of mutations in birds. Our analysis therefore highlights the bird d N /d S ratio as a molecular evolutionary paradox and a challenge for future research.