STELLWAG, Edmund/J; SETHI, Pooja/R; HOCHBERG, Robert; SCEMAMA, Jean-Luc; East Carolina University; East Carollina University; East Carolina University; East Carolina University: Evolution of developmental gene cis-regulatory elements

We developed a computational method for the identification of putative cis-regulatory elements, which incorporates a direct measure of the effects of selection as a determinant in non-protein coding sequence evolution. As such, the method provides a biologically relevant framework for comparisons of non-protein coding sequence evolution. Comparisons of orthologous HoxA, Aa and Ab cluster paralogous group 2 intergenic and intron-related sequences from Mus musculus(mouse), Homo sapiens (humans), Heterodontus francisci (horn shark), Polypterus senegalus (bichir), Danio rerio (zebrafish), Oreochromis niloticus (Nile tilapia), Morone saxatilis (striped bass), and Takifugu rubripes (Japanese pufferfish) revealed three sequence domains that are under purifying selection in all the species and on both clusters, indicative that these three regions likely represent fundamental regulatory control elements of HoxA cluster paralogous group 2 genes in their common gnathostome ancestor. Detailed analysis of one of these three domains using both Mus musculus and Morone saxatilis HoxA paralogous group 2 regions as the index for comparisons demonstrated the presence of four general gnathostome elements, one general actinopterygian element, two general teleost elements and a host of mammalian and perciform-specific elements. The results also showed the partitioning of cis-regulatory elements between the actinopterygian HoxAa and Ab clusters relative to the inferred ancestral gnathostome HoxA cluster. Overall, our results indicate that the evolution of Hox paralogous group 2 cis-regulatory regions is dominated by the evolution of novel lineage-specific elements superimposed on a framework of shared common ancestral elements.