When Is Selection Effective?

Deleterious alleles can reach high frequency in small populations because of random fluctuations in allele frequency. This may lead, over time, to reduced average fitness. In this sense, selection is more "effective" in larger populations. Recent studies have considered whether the different demographic histories across human populations have resulted in differences in the number, distribution, and severity of deleterious variants, leading to an animated debate. This article first seeks to clarify some terms of the debate by identifying differences in definitions and assumptions used in recent studies. We argue that variants of Morton, Crow, and Muller's "total mutational damage" provide the soundest and most practical basis for such comparisons. Using simulations, analytical calculations, and 1000 Genomes Project data, we provide an intuitive and quantitative explanation for the observed similarity in genetic load across populations. We show that recent demography has likely modulated the effect of selection and still affects it, but the net result of the accumulated differences is small. Direct observation of differential efficacy of selection for specific allele classes is nevertheless possible with contemporary data sets. By contrast, identifying average genome-wide differences in the efficacy of selection across populations will require many modeling assumptions and is unlikely to provide much biological insight about human populations.