On the other hand, insertions and deletions dominate mutational screens in Drosophila, and a large number map to noncoding intergenic and intronic regions. This is exemplified by the intensively studied bithorax complex, where there are not only mutations known in the coding sequences for the homeotic protein Ultrabithorax (Ubx), but also in upstream (bithoraxoid or bxd) and intronic (Contrabithorax or Cbx and anterobithorax or abx) sequences [124], which contain conserved blocks within them [125]–[127]. Such noncoding mutations are interpreted as affecting orthodox cis-acting enhancer sequences (i.e., those that bind cis-acting regulatory proteins), despite the fact that (for example) bxd mutations fall within a region that is transcribed during early embryogenesis into a complex set of short polyadenylated RNAs with no coding potential. These RNAs arise by alternative splicing of at least 11 exons derived from a 26-kb primary transcript [126]. Moreover, these regulatory regions involve interaction with Polycomb-group and Trithorax-group proteins, which are increasingly implicated as being directed to their sites of action by ncRNAs [7],[13],[128] (see below).
