We examined negative selection using two measures that highlight different periods of selection in the human genome. The first measure, inter-species, pan-mammalian constraint (GERP-based scores; 24 mammals8) addresses selection during mammalian evolution. The second measure is intra-species constraint estimated from the numbers of variants discovered in human populations using data from the 1000 Genomes project55 and covers selection over human evolution. In Figure 1, we plot both these measures of constraint for different classes of identified functional elements, excluding features overlapping exons and promoters that are known to be constrained. Each graph also shows genomic background levels and measures of coding-gene constraint for comparison. Since we plot human population diversity on an inverted scale, elements that are more constrained by negative selection will tend to lie in the upper and right hand regions of the plot.
