THE DEGREE OF VARIATION IN DNA-SEQUENCE RECOGNITION AMONG 4 DROSOPHILA HOMEOTIC PROTEINS

The homeodomain has been implicated as a major determinant of biologic al specificity for the homeotic selector (HOM) genes. We compare here the DNA sequence preferences of homeodomains encoded by four of the ei ght Drosophila HOM proteins. One of the four, Abdominal-B, binds prefe rentially to a sequence with an unusual 5'-T-T-A-T-3' core, whereas th e other three prefer 5'-T-A-A-T-3'. Of these latter three, the Ultrabi thorax and Antennapedia homeodomains display indistinguishable prefere nces outside the core while Deformed differs. Thus, with three distinc t binding classes defined by four HOM proteins, differences in individ ual site recognition may account for some but not all of HOM protein f unctional specificity. We further show that amino acid residues within the N-terminal arm are responsible for the sequence specificity diffe rences between the Ultrabithorax and Abdominal-B homeodomains. Similar ities and differences at the corresponding positions within the N-term inal arms are conserved in the vertebrate Abdominal-B-like HOM protein s, which play critical roles in limb specifications as well as in regi onal specification along the anterior-posterior axis. This and other p atterns of residue conservation suggest that differential DNA sequence recognition may play a role in HOM protein function in a wide range o f organisms.