Figure 4

A two-step scenario for the H2 duplication in vertebrate COE proteins. (A) Exon-intron structure of the H1-H2a HLH motif in the coe ancestor gene; the phase of introns is indicated, with phase 0 introns in red and phase 1 introns in black. (B) The first step in H2 duplication was a duplication of the exon encoding H2a. Because of the splice phase rule, this could only result in alternative splicing out either the ancestral (H2a, dotted angled line) or the newly created exon (H2d, solid angled line). (C) The second step was the activation of a cryptic 3' splice donor site, downstream of the H2d coding region (blue arrowhead). This resulted in same phase i11 and i12 introns and the incorporation of H2d into COE proteins (D). Note that H2d exon-skipping can theoretically occur (dotted angled line).