The University Record, January 16, 1996

Fruit fly study may help explain genetic development

By Sally Pobojewski
News and Information Services

 A U-M biologist has discovered that subtle variations in "master control" genes which regulate embryonic development in animals are responsible for the fact that most of us end up looking pretty much the same.

"Birth defects like cleft palate, hunchback and thalidomide-induced abnormalities are thankfully rare, in part because variation in these genes helps protect developing embryos from the effects of a harsh and dangerous environment," says Gregory C. Gibson, assistant professor of biology. Gibson spent two years looking for solutions to the mystery of developmental stability by studying the effects of a gene called Ultrabithorax (Ubx) on the body structure of fruit flies.

The results of experiments conducted by Gibson and D.S. Hogness of the Stanford University School of Medicine were published in the Jan. 12 issue of Science. It is the first study to document specific biological effects produced by modifying the regulatory genes which control the earliest stages of animal development.

"Much like the architect on a major construction project, these genes work by coordinating the activity of other genes---turning them on and off at precise times and locations in the developing embryo," Gibson says. Found in all types of animals from fruit flies to people, these ancient genes evolved around 600 million years ago and probably were responsible for the surge in evolutionary diversification occurring on Earth at that time.

Fruit flies have one regulatory gene for each body segment, Gibson explains. In a famous series of experiments during the 1970s, E.B. Lewis discovered that knocking out the Ubx gene produced four-winged flies with the back of the thorax transformed into a second copy of the middle of the thorax. "It was as if the architect went to the wrong building site," Gibson says.

"If Lewis was able to produce major differences in appearance by removing the Ubx gene completely," Gibson adds, "I wondered what might happen if the gene was modified slightly."

To find out, Gibson repeated an experiment conducted 50 years ago by the British biologist C.H. Waddington. When he exposed fruit fly embryos to ether vapor, Waddington selected a strain of four-winged flies, which passed the trait on to later generations not exposed to ether.

Using a specific strain of fruit flies, Gibson and Hogness repeated Waddington's experiment by exposing embryos to ether vapor for 10 minutes, selecting adults with abnormalities in their third thoracic segment, and breeding them with other affected adults for eight generations.

"We saw a steady increase in the frequency of thoracic abnormalities called phenocopies in each generation from 13 percent in the starting population to a plateau of 45 percent," Gibson says. Conversely, when Gibson selectively bred non-transformed flies resistant to ether treatment, the frequency of thoracic abnormalities dropped steadily.

"Waddington's experiment showed some fruit flies were more sensitive to ether-induced phenocopies than others, but he had no idea why," Gibson says. "In our experiment, we show that differences in the Ubx gene are the cause of these morphological changes."

Identifying the genetic cause of specific changes in a simple organism like fruit flies may help scientists understand how multiplegene interactions may make some people more susceptible to heart disease, mental disorders or cancer, according to Gibson.

Gibson's research was conducted at the Stanford University School of Medicine with support from the National Institutes of Health.