Duplicated most conserved elements. (a) A schematic illustration of three classes of dMCEs in a hypothetical two-exon gene is shown. The blue rectangles represent exons of three different two-exon genes, and the red arrows represent the relationship between pairs of duplicated MCEs relative to their gROIs. GeneA1 and GeneA2 are paralogs in the same gene family, whereas GeneB represents an unrelated gene. The figure shows a local dMCE pair in the same gROI upstream from GeneA1, an intronic pair of dMCE elements between the paralagous gROI of GeneA1 and GeneA2, and an intergenic pair of dMCE elements downstream unrelated genes GeneA2 and GeneB. (b) Example of a dMCE pair between unrelated genes CAST1 (chromosome 3) and SNAP25 (chromosome 20) is shown. The pair involves an element in the first intron of CAST1(.789) and an element in the last intron of SNAP25(.157). Orthologous species shown in the alignments include chimpanzee (Pan troglodytes [pt]), dog (Canis familiaris [cf]), mouse (Mus musculus [mm]), rat (Rattus norvegicus [rn]), chicken (Gallus gallus [gg]), and zebra fish (Danio renio [dr]). Both elements are conserved in mammals, and SNAP25 element exhibits conservation in chicken and zebrafish. Both genes related to these elements exhibit increased expression in brain tissues, and reduced expression in immune tissues and cell types. Both genes also show increased expression in hippocampus and throughout the cortex, although they differ in cerebellum expression as shown by in situ expression patterns courtesy of Allen Brain Atlas . dMCE, duplicated most conserved element; gROI, genomic region of interest.