Inference of the distribution of selection coefficients for new nonsynonymous mutations using large samples

The distribution of fitness effects (DFE) has considerable importance in population genetics. To date, estimates of the DFE come from studies using a small number of individuals. Thus, estimates of the proportion of moderately to strongly deleterious new mutations may be unreliable because such variants are unlikely to be segregating in the data. Additionally, the true functional form of the DFE is unknown, and estimates of the DFE differ significantly between studies. Here we present a flexible and computationally tractable method, called Fit{partial}a{partial}i, to estimate the DFE using the site frequency spectrum from a large number of individuals. We apply our approach to the frequency