Selection at conserved vs. nonconserved nucleotide positions (EGP). Effect of partitioning genomic sequence features into conserved and nonconserved positions on nucleotide diversity and allele frequency distributions. Only EGP SNPs at non-CpG sites were considered. (a) Nucleotide diversity (π; vertical axis) in exons, CNSs defined by PhastCons, introns, introns aligning between chimp and dog but not between chimp and rodents, intergenic sequences, intergenic sequences aligning between chimp and dog but not between chimp and rodents, and all non-CNS noncoding sequences. (b) Nucleotide diversity at conserved (green) and nonconserved (orange) positions within genomic features shown in a. P values (Fisher exact test) for differences in density of segregating sites between conserved and nonconserved positions at corresponding features are shown. (c) Fraction of SNPs with derived allele <1% (vertical axis) within different genomic sequence features. (d) Fraction of SNPs with derived allele <1% at conserved (blue) and nonconserved (red) positions within features shown in c, with corresponding P values. Semitransparent data indicate features for which the number of SNPs within the EGP data set do not provide sufficient power to detect statistically significant differences in allele frequency distribution.

Selection at conserved vs. nonconserved nucleotide positions (HapMap). Effect of partitioning genomic sequence features into conserved and nonconserved positions on HapMap allele frequency distributions (non-CpG sites). (a) Fraction of rare derived alleles (frequency <5%; HapMap Yoruba data set) in genomic sequence features (see legend to Fig. 1 for details). (b) Fraction of SNPs with derived allele <5% at conserved (blue) and nonconserved (red) positions within features shown in a, with corresponding P values.

Distribution of 4GCBs relative to CNSs. CNSs are typically defined by lengths of human genomic sequence in which the percent human–mouse sequence identity exceeds a threshold value. Shown, for each combination of length (50–200 bp) and percentage of human–mouse sequence identity (60%–90%) (a) or various other CNS definitions (b), is the fraction of the human genome encompassed by that CNS definition (range 30.8% to 0.8%) over the fraction of 4GCBs that fall outside of this definition (range 17.6% to 96.4%). For comparison, parameters used in previous studies of CNSs are highlighted in yellow (34) and red (17). The PhastCons CNS definition is the one used to generate Figs. 1 and 3.

Fraction of functionally significant nucleotide positions among 4GCBs. (a) Fraction of functional sites under selection (y axis) sufficient to explain the observed excess of rare alleles in conserved positions, expressed as a function of selection coefficient (x axis; logarithmic scale) for three different population histories. The fraction of functional sites exhibits a minimal value (under any possible strength of selection) needed to explain the observed shift in allele frequency distribution. This minimum provides a lower limit estimate of the fraction of functional sites. (b) Allele frequency distributions for SNPs in non-4GCB (red) and 4GCB intronic positions (light blue) are shown in parallel with theoretical distributions (corresponding to the optima from a) for neutral SNPs (purple) and a mixture of neutral SNPs and functional SNPs (dark blue).