Human GRB encompassing PAX6 and bystander genes (middle track) and the two duplicated zebrafish loci. The human locus spans >1 megabase (Mb) and contains the PAX6 target gene (in red) and five bystander genes (green). Highly conserved noncoding elements (HCNEs) conserved from human to zebrafish are denoted as blue ovals. Note that some HCNEs are conserved in both zebrafish loci, but that most are only conserved in one locus, leading to subfunctionalization. Bystander genes are usually conserved in one copy only. In the upper part of the figure, two insertions in zebrafish pax6 genomic regulatory blocks (GRBs) take on the correct expression pattern of the orthologs, although CLGY825 is 120 kb downstream of pax6.1, next to the bystander zcsl3, whereas CLGY954 is inserted inside the bystander gene elp4, downstream of pax6.2. Note also the complementarity of reporter expression. Although pax6.1 is strong in diencephalon and hindbrain, pax6.2 retains stronger expression in retina, pineal, and spinal cord. For more details, see Kikuta and coworkers .