Module: Homeotic Genes
The human body is composed of several trillion
cells. All of them originate from the same single fertilized egg, yet almost all
of them have become specialized to perform certain tasks. But all of the body’s
cells (except for the lymphocytes) contain the same genes, so how does one cell
become a nerve cell rather than, say, a liver cell? This question troubled biologists
for many years.
The answer lies in the fact that not all the genes in
a cell are activated at the same time. Some proteins in the nuclei of cells will,
by binding to their DNA, trigger the expression of only certain genes of this
DNA. And the product of these particular genes will be a protein whose function
will contribute to making the cell more specialized.
Several of the proteins
that can bind to DNA come from genes which, when expressed, give the cell a specialty
specific to its position in the body. The term homeotic genes
designates these genes that encode proteins that bind to specific sequences of
DNA and thus influence the organism’s subsequent development.
These specific sequences of DNA are called homeoboxes. The proteins
that arise from a gene containing a homeobox sequence can bind to another gene
in turn, thus triggering a cascade of gene expressions resulting in the segmentation
of the embryo.
We thus can see how certain “master” homeotic
genes control the transcription of a set of secondary genes that in turn influence
the activity of other target genes at a lower level in the hierarchy. These genes
will then produce the proteins used to build the structures and organs of the
Certain genes that contain the homeobox sequence, the hox
genes, are grouped one after the other along certain chromosomes (see diagram
to right). In addition, the order of this alignment reflects the positions of
the body parts that these genes control. Through the regulatory proteins that
they produce, the hox genes orchestrate the entire anatomical structure of the
body, including the nervous system.
Because the homeobox sequence has remained almost unchanged
over millions of years of evolution in many species, homeotic genes would appear
to play a vital role in the general organization of the body in almost all animals,
including worms, flies, birds, mice, and humans.
Source: Dr. Rudi Turner
normal (left) and with Antennapedia mutation (right)
When the function of a homeotic gene is disturbed by a genetic mutation, entire
parts of the body can develop at the wrong location. There are several known examples
of these “homeotic”mutations, such as the Antennapedia mutation, in
which the Drosophila fly develops legs where its antennae should be (see photo).
This mutation is due to the expression of the Antennapedia gene at a site that
is too anterior, which causes an anterior segment to be transformed into a normally
In the human brain, certain developmental disorders, such
as autism and various forms of mental retardation, are associated with mutations
of the homeobox genes.