Positive control. Distribution of fitness effects (DFE) for non-fourfold degenerate ESE sites, using fourfold degenerate non-ESE sites as control. (Blue zone) Effective neutrality; (light yellow zone) very weak negative selection; (dark yellow zone) weak to strong negative selection. “No filtering,” “human filtering,” and “ancestral filtering” refer to different methods for filtering out CpG dinucleotides (for more details, see main text).