Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection
(a) 58 human DHS gains (yellow arrow) overlapped human upregulated genes (HumanExpUp), a highly significant enrichment compared to 100,000 random permutations (P = 0.00039). Only 17 human DHS gains (blue arrow) overlapped human downregulated genes (HumanExpDown), which is lower than random permutations (P = 0.008) (b) Comparison of DHS gains and losses with expression gains and losses. Yellow represents DHS and expression matches that occur more often than random permutations, while blue represent less often. P value indicated in each box. (c) Percentage of regions that display evidence of positive selection on the human (purple) or chimpanzee (brown) branch. Both human-specific DHS site gains and losses show more evidence of positive selection on the human branch, while chimpanzee-specific DHS site gains and losses show more evidence of positive selection on the chimpanzee branch (*P<0.03, ** P<0.002). Common sites show an equivalent amount of selection on both branches. (d) Percentage overlap of DHS Gains (combined from both human and chimpanzee), DHS Losses, and Common DHS sites compared to evolutionarily constrained regions generated using GSC (Materials and Methods). Regions were divided into three compartments: promoter, intron, and intergenic regions. The black dot represents the null expectation of finding a constrained region and error bars represent one standard deviation.