(A) Four specific examples of population-stratified CNVs intersecting genes are shown, including LRRIQ3, the pancreatic collipase CLPS, the sperm head an acrosome formation gene DPY19L2, and the haptoglobin and haptoglobin-related genes HP and HPR. Dot-plots indicating the copy of the locus in each individual and pie charts with colors depicting the continental population distribution per copy number (see text for details and Figs. 1 and 2 and dot plots for color scheme). (B) Predicted copy number on the basis of read-depth for a 73.5 kbp duplication on chromosome 16. It is observed in the archaic Denisovan genome and at 0.84 allele frequency in Papuan and Bougainville populations, yet absent from all other assessed populations. The duplication intersects two microRNAs. The orange arrow corresponds to the position and orientation of this duplication as further highlighted in (C) and (D). (C) A heatmap representation of a ~1 Mbp region of chromosome 16p12 (chr16:21518638-22805719). Each row of the heatmap represents the estimated copy number in 1 kbp windows of a single individual across this locus. Genes, annotated segmental duplications, and arrows highlighting the size and orientation in the reference of the Denisova/Papuan-specific duplication locus (locus D) and three other duplicated loci (A, B, and C) of interest are shown below. (D) The structure of duplications A, B, C and D (as shown in 4C over the same locus) in the reference genome and the discordant paired-end read placements used to characterize two duplication structures. Structure A/C is found in all individuals, though not present in the reference genome, while structure B/D is only found in Papuan and Bougainville individuals indicating a large complex, duplication (~225 kbp) composed of different segmental duplications. Both the A/C and B/D duplication architectures exhibit inverted orientations compared to the reference. The number of reads in all Oceanic and non-Oceanic individuals supporting each structure are indicated. (E) Maximum likelihood tree of the 16p12 duplication locus (duplication D in 4B, 4C, and 4D) constructed from the locus in Orangutan, Denisova, the human reference and the inferred sequence of the Papuan duplication (24). All bootstrap values are 100%.