The impact of non-neutral synonymous mutations when inferring selection on non-synonymous mutations.

The distribution of fitness effects (DFE) describes the proportions of new mutations that have different effects on reproductive fitness. Accurate measurements of the DFE are important because the DFE is a fundamental parameter in evolutionary genetics and has implications for our understanding of other phenomena like complex disease or inbreeding depression. Current computational methods to infer the DFE for nonsynonymous mutations from natural variation first estimate demographic parameters from synonymous variants to control for the effects of demography and background selection.