Similarities Among Developmental Genes
The sequences of the fushi tarazu and Antennapedia
genes revealed that they encoded protein, and more importantly, that over a
stretch of about 60 amino acid residues, the sequences of the two proteins were
even more highly conserved than the corresponding coding DNA sequences. A
portion of another homeotic developmental gene complex, bithorax, also
possessed a closelrelated sequence. This sequence is now called a homeo box.
With the conservation of the homeo box among three proteins, it seemed likely
to be present in other developmental regula-tors from the fly as well as in
closely related organisms. This proved to be true. Not only do other species of
Drosophila contain homeo boxes; so do
all higher organisms, including humans. Typically a Southern transfer of
genomic DNA hybridized to a homeo sequence reveals five to ten similar
sequences. If hybridization at low stringency is performed, less closely
related sequences are revealed. These have been cloned and sequenced, yielding
the expected more variable homeo-like sequences. Such sequences can be used
again to find still less closely related genes. Many organisms possess multiple
clusters of four or five homeo box proteins.
Homeo boxes were also noticed to be similar to the
alpha mating-type factors of yeast which were known to bind to DNA. Therefore
it seemed likely that proteins containing a homeo-box sequence bind to DNA.
This is true. Homeo-box domains bind DNA, and the structure of several has been
determined. The homeo-box fits into the major groove of the DNA, but its
positioning is notably different from that of the helix-turn-helix motif. Not
all developmental genes possess homeo boxes. A number of other DNA-binding
motifs are utilized, including zinc finger, zinc do-mains, helix-loop-helix
proteins and others.