Transgenics

What Can Flies with Eyes on Their Legs Tell Us About Gene Regulation?
From time to time, we hear reports of strange scientific experiments that make us wonder, "Why on earth would anyone want to do that?" One example occurred in 1995, when newspapers, magazines, and newscasts reported the existence of some very bizarre flies in Switzerland. Using genetic engineering techniques, Swissresearchers, led by Walter Gehring, had produced flies with additional eyes. Instead of the normal situation in which the fly has two eyes, each properly located on the side of the head, these genetic anomalies had eyes on their knees, their antennae, their wings, and other strange places. One fly had fourteen “eyes” located in various positions on its body! When people heard this report, they imaginedstories of Frankenstein and other mad scientists of Western literature—who else would attempt such a feat? However, the real question the researchers were asking had nothing to do with creating a “visually-endowed” fly. Instead, it dealt with the most fundamental nature of how genes determine the structure of body parts in organisms. And the way they answered the question was elegant andstraightforward.
During development of a multicellular organism, whether it is a fly or human, specific genes must be turned on in a temporally programmed series. This hierarchy of gene expression enables cells to adopt their ultimate location, shape, and function within the developing organism. In the case of eye development, about 2,000 different genes must be “turned on” at the proper time and place foreyes to develop properly. Such genetic “pyramid schemes” underlie the formation of all tissues and organs in multicellular organisms. A good illustration of this process is to consider a complex array of dominoes, each poised to topple one or more other dominoes set up nearby. When one domino falls, a chain reaction occurs in which dozens or hundreds of other dominoes also fall, in a specified timingand order. When the whole event is over, the pattern of dominos that have fallen versus those that have been left standing depends on which initial domino was toppled.
In organisms, the first "dominoes" in a gene regulation pyramid are sometimes called master control genes. These genes encode proteins that bind to the control regions of other genes and turn them on (i.e., activatetranscription). As a result, a second tier of genes is activated, many of which also activate expression of a third tier of genes. The process continues in a kind of genetic chain reaction until, ultimately, the set of proteins that are uniquely expressed in that particular cell is activated. For example, in red blood cells, hemoglobin must be produced since it carries oxygen and carbon dioxide. In eyes, theprotein rhodopsin must be produced since it is the primary light receptor.
What are the master control genes that stimulate eye development? For such developmental questions, the fruit fly, Drosophila melanogaster, is a wonderful experimental organism. Mutant flies had been discovered that lack eyes altogether. The defective gene in these flies was identified and given the rather obvious name,“eyeless.” The eyeless gene was cloned and its DNA sequence was determined. Now, the fun began in earnest. There are massive databases on the World Wide Web in which researchers throughout the world deposit information about the sequences of the genes they have discovered. In fact, it is typically a requirement of the publishers of scientific journals that information about a gene’s sequence is placedin these amazing resources. The most common one is GenBank, a database managed by the U.S. National Center for Biotechnology Information. This information is an incredible boon to genetic research because it lets a researcher compare a gene sequence they are studying to that of ALL OTHER known genes on the planet. In many cases you can get clues about what your gene is doing by learning what it...