Extended Data Fig. 7 |. GC content cannot explain differences in singleton enrichment between tissues.

a, We partitioned the site frequency spectra of enhancers into SNPs that have GC ancestral alleles and SNPs that have AT ancestral alleles. Using each of these disjoint variants sets, we then computed singleton enrichment in enhancers versus adjacent control regions. GC-biased gene conversion is expected to have opposite effects on the two frequency spectra, increasing the proportion of GC-ancestral singletons and decreasing the proportion of AT-ancestral singletons. Despite this confounder, the finding that brain enhancers are enriched for singletons holds up when we restrict to either GC-ancestral SNPs or ATancestral SNPs. b, Across tissues, enhancers are enriched for GC base pairs compared to adjacent genomic regions. However, there is no correlation between GC content enrichment and the singleton enrichment that we attribute to purifying selection.