Fig. 1

HYDIN duplication and evolution. a Comparison of human genomic sequence from the donor locus on chromosome 16q22.2 (top) to the acceptor locus on chromosome 1q21.1 (middle) shows a 364 kbp duplication (blue lines) including exons 6-84 of the 86-exon ancestral gene HYDIN, visualized using Miropeats [74]. Connecting lines indicate nearly identical segments (s = 1000). The orthologous insertion site (bottom) prior to insertion based on sequencing of chimpanzee BAC (CH251-231E10) is shown with homology indicated (green lines). Human gene annotation (GENCODE) as well as the location of the exons found in fusion transcripts, breakpoints (dashed boxes), and acquired novel promoter (arrowhead) are depicted. b Sequence alignment of the 5' and 3' breakpoints (dashed red boxes) shows that the duplication integrated at the boundary of an LTR and LINE repeat with the concomitant loss of 841 bp of LINE sequence based on analysis of the chimpanzee orthologous sequence. Uppercase bases are beyond the breakpoint while lowercase bases indicate a break in homology. Numbers are as indicated in (a). c A neighbor-joining phylogenetic tree based on a 315,349 bp MSA using the human paralogs as well as orthologous chimpanzee and orangutan sequences. Based on the genetic distance (Kimura 2-parameter) and assuming a human–chimpanzee divergence of 6 million years ago (mya), we estimate the duplication occurred ~3.17 mya (95% CI: 3.09–3.24 mya, bootstrap method). d The model depicts the simplified evolutionary history of the HYDIN2 genomic locus as a series of juxtaposed segmental duplications that contributed novel exons and regulatory machinery. Human-mouse comparative sequence analysis (GRCh38/GRCm38) shows that the 5' and 3' exon blocks (yellow arrows) originated as a single ~89 kbp segmental duplication mapping to human chromosome 1p22.3. It was duplicated in the common ape ancestor (21 mya) from chromosome 1p22.3 to chromosome 1q21.1 in close proximity to the NBPF core duplicon and the promoter-containing segment of HYDIN2 (green arrows). Approximately 3.2 mya, an inverted duplication (109 kbp) occurred with NBPF cores defining the breakpoints at chromosome 1q21.1 and 1q21.2. This was followed by the insertion of the 364 kbp HYDIN segmental duplication from chromosome 16q22.2. See Additional file 1: Figure S2 for phylogenetic analyses. e Miropeats (s = 800) schematic shows the genomic organization of the segmental duplications and surrounding gene annotation. This includes the 364 kbp HYDIN segment (blue), the 89 kbp exon-containing segment from chromosome 1p22.3 (yellow), and the larger, 109 kbp, inverted segmental duplication, shared with between chromosome 1q21.1 and chromosome 1q21.2 (green and yellow). Inset shows DHS data for fetal brain in the ~14 kbp surrounding the first exon of HYDIN2. The new promoter (bent arrow) corresponds to a peak of chromatin accessibility (see also Additional file 1: Figure S6, Table S8)