Homeobox
Since their discovery by David Hogness in the genome of the fruit fly Drosophila melanogaster in 1983, homeobox genes, and the proteins they encode the homeodomain proteins, have turned to play important roles in the developmental processes of many multicellular organisms.
The first homeobox identified in Drosophila was described as a conserved DNA region of about 180 base pairs. It is found on eight different sites on the third chromosome, a chromosome known to be central to developmental processes. These genes found to encode homeodomain proteins were developmental proteins, in particular homeotic genes, from which the name homeo box was derived.
The next homeobox gene was found in frogs. Its sequence is almost identical to that of the fruit fly. More organisms were studied and the same DNA sequences were found in earthworms, beetles, mice, chickens, cows, sea urchins, yeast, plants, nematodes, and even though humans are separated from insects by over 600 million years of evolution, people. This ubiquity for the sequence supports the hypothesis of a common ancestor for life.
The homoebox genes are crucial in the early steps in the development of embryos, such as determining the anterior posterior orientation of the egg of D. melanogaster. They also have a crucial role in the cell differentiation that occurs very late in organism development--such as neuron differentiation in the nematode Caenorhabditis elegans.
The developmental control arises from the binding of the homeodomain proteins to DNA. In binding to DNA they regulate the transcription of other genes. Thus, they are transcription factors. As with other DNA-binding proteins, the homeobox proteins have a distinctive shape, described as helix-turn-helix. The shape allows the protein to literally grab onto the DNA. In Drosophila, and similarly in other organisms, this binding activates genes that produce proteins responsible for cellular specialization.
Homeobox genes, also called "hox" genes, are responsible for the big decisions of development rather than the finer details of engineering. Fruit flies with a particular mutation in one of their many hox genes will develop an anatomically normal leg in the spot where an antenna should be.
In humans, defect in the homeobox causes various developmental abnormalities. Studies of family members having abnormalities in their thumbs and big toes identified a mutation in one of the homeobox genes. Similar mutations in experimental mice cause digital and genital abnormalities. Another human condition shown to be caused by defective hox genes is craniosynostosis--a condition in which the skull joints fuse prematurely, leaving the brain scant room to grow. The molecular explanation may be defect in apoptosis--programmed and targeted cell death--which is a requirement for normal development of many systems, including the skull.
Because of the association of hox genes with programmed cell death, researchers now suspect that the genes may play a role in uncontrolled cell growth--cancer. Failure of cells to shift to the self-destruct mode triggers tumor growth in several types of cancer, and has an effect on whether cancer spreads from one part of the body to another.
This is the complete article, containing 489 words
(approx. 2 pages at 300 words per page).
