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2002 > March
Fly by genetics
Tiny fruit fly offers clues to human genome
A the end of a corridor on the first floor of Barnum Hall is a lab with shelves and tables covered with boxes containing dozens and dozens of test tubes. Inside the test tubes, capped with cotton, tiny fruit flies flit around, sometimes resting on the dark brown material in the bottom of the tube that is their food.
Victoria Meller, assistant professor of biology, along with graduate student Barbara Rattner and department staff, spend countless hours monitoring and studying the flies to learn more about genetics. The fruit flies—familiar to anyone who has left an overripe banana sitting on the kitchen counter too long—are known to the scientific community as Drosophila melanogaster. Scientists have used the tiny flies to study genetics for 90 years because they hold lessons that can be extrapolated to mammals.
New insights into RNA
Dosage compensation is an essential process in which an entire chromosome is regulated. "If an animal gets an extra chromosome or loses part of a chromosome, there are terrible problems associated with it," explains Meller. "We need the entire genetic complement, but we don't want any more. An example is Down syndrome, which is an example of having an extra chromosome."
In mammals, females have two X chromosomes, and males have one X and one Y. To regulate the number of X chromosomes, the female randomly selects one X chromosome and silences it. In Drosophila, the females also have two X chromosomes and the male one X, but here the process is the opposite. The female does nothing, and the male doubles the activity of the X.
Initially, Meller says, "we thought the processes in the Drosophila and mammals would have nothing in common. But in both systems, the organism must be able to identify one chromosome out of the whole set of chromosomes and regulate it."
Understanding gene regulation
But the major discovery in Meller's work was the conclusion that RNA molecules participate in the process of dosage compensation.
"The dogma of biology," says Rattner, "is that you have the DNA sequence transcribed into an RNA molecule, which functions as an intermediate or template to the protein, which is the functional molecule. But now we are finding RNA molecules that have a function other than as the coding for protein. It's a new field in biology to study functional RNA and its properties and functions."
Meller's lab is studying two RNA molecules that code for no protein. Her paper shows that these two RNA molecules are redundant and essential components of the dosage compensation machinery in male fruit flies. If you eliminate just one, nothing happens, and the other seems to compensate. But if you eliminate both, it is lethal for the males, because dosage compensation does not work properly.
Like us in many respects
For many years, the fruit fly was believed to have little relevance for the understanding of human genetics. But in the mid-1980s, scientists began to learn that there are amazing similarities between Drosophila genes and human genes. Fruit flies have approximately 12,000 to 15,000 genes compared with some 30,000 to 50,000 genes for humans. Humans share a large number of homologous genes with flies because of the degree of gene duplication that occurred as higher organisms evolved. Because fruit flies have been studied for so many years, there is a large reserve of genetic information available about them.
Meller's lab will continue to further the understanding of dosage compensation as well as the role of RNA. "It is only in the last few years," said Rattner, "that we are finding that RNA molecules have interesting and unrevealed functions."