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Genome-Wide Inference of Ancestral Recombination Graphs

Figure 6

Mean allele age as a function of annotation class and derived allele frequency.

(A) Estimated age of derived allele in generations, averaged across polymorphic sites of various annotation classes. Estimates were derived from ARGs sampled by ARGweaver based on the Complete Genomics data set (see Methods). Error bars represent one standard deviation above and below the mean. Neut = putatively neutral sites; 4d = fourfold degenerate sites in coding regions; CNS = conserved noncoding sequences identified by phastCons; PPh:{Benign,PosDam,ProbDam} = missense mutations identified by PolyPhen-2 as “benign”, “possibly damaging”, or “probably damaging”, respectively; CV:{NonPath,Path} = mutations in “nonpathogenic” (categories 1–3) or “pathogenic” (categories 4 & 5) classes in the ClinVar database, respectively. (B) Similar plot with categories further divided by derived allele frequencies (DAF) in numbers of chromosomes out of 108. Error bars represent 95% confidence intervals, as assessed by bootstrapping. In categories that combine multiple frequencies (e.g., 4–5, 6–8), a subsampling strategy was used to ensure that the relative contributions of the different frequencies matched those of the Neut class. Estimates for DAF>20 were excluded due to sparse data. Notice that ages generally increase with DAF, as expected (see Supplementary Figure S7), but at a considerably reduced rate in categories under strong selection.

Figure 6