HIV-1–dependency genes identified by genome-wide short interfering RNA (siRNA) screens are relatively conserved. (a) Selection as measured by the ratio of nonsynonymous substitutions per nonsynonymous site (dN) to synonymous substitutions per synonymous site (dS) across primate species for 99 high-confidence HIV-1 dependency factors (HDFs) (dashed line) and a background set of 16,618 genes (solid line). HDFs are relatively depleted of nonsynonymous variation (Wilcoxon rank sum P = 0.01), suggesting conservation across species. (b) Example plot summarizing human variation across the HDF PARP9 in a set of ~6,300 individuals from the NHLBI ESP. The protein background (gray box) is plotted with vertical bars indicating amino acid location of protein-modifying variants (blue, missense; red, stop-gain (nonsense); yellow, frameshift). Amino acid locations of stop-gain and frameship variants are given below the protein background Top, bars indicate the frequency of each plotted variant (green, rare variants; purple, common variants). This variation could be exploited to test the importance of the encoding gene in HIV-1 replication ex vivo. Protein plot was generated by the GuavaH web tool. MAF, minor allele frequency.