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Genome-Wide Inference of Ancestral Recombination Graphs

Figure 5

Measures of genetic variation near protein-coding genes and partial selective sweeps.

Shown (from top to bottom) are nucleotide diversity (), time to most recent common ancestry (TMRCA), and relative TMRCA halflife (RTH) for the 13 individuals (26 haploid genomes) of European descent (CEU and TSI populations) in the Complete Genomics data set (similar plots for African population are shown in Supplementary Figure S11). Nucleotide diversity was computed as the average rate of nucleotide differences per site across all pairs of chromosomes, whereas sitewise values of the TMRCA and RTH were computed by averaging over local trees sampled by ARGweaver. (A) Estimates for 17,845 protein-coding genes from the Consensus Coding Sequence (CCDS) track in the UCSC Genome Browser (hg19). Estimates for noncoding regions were computed by averaging in a sliding window of size 300 bp then averaging across genes. Estimates for coding exons were computed by first averaging over fourfold degenerate (4d) sites of each exonic type (first, middle, last), then averaging across genes (see Methods). Only 4d sites were considered to focus on the influence of selection from linked sites rather than direct selection. Nevertheless, the decreased values for the exons suggest some influence from direct selection. The differences between exons and flanking sites may also be influenced by windowing in the noncoding regions. “First exon” is taken to begin at the annotated start codon and “last exon” to end at the stop codon, so that both exclude untranslated regions. The TMRCA is measured in thousands of generations. RTH is ratio of the time required for the first 50% of lineages to find a most recent common ancestor to the full TMRCA (see Supplementary Figure S10). Error bars (dashed lines for noncoding regions) indicate 95% confidence intervals as estimated by bootstrapping over regions. (B) Similar plots for 255 100-kb regions predicted to have undergone partial selective sweeps in the CEU population based on the iHS statistic [72]. In this case, all measures are computed in a sliding window of 10,000 bases. Notice that both protein-coding genes and putative selective sweeps display substantial reductions in nucleotide diversity, but the genes show a much more prominent reduction in TMRCA, whereas the sweeps show a much more prominent reduction in RTH. These signatures are consistent with a dominant influence from background selection rather than hitchhiking in protein-coding genes (see text).

Figure 5