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Scientists discover that genetic changes result mostly from many small contributors

First fruits of the genome project identify genes in flies bred for a behavioral preference

The Neurosciences Institute

SAN DIEGO - From Triple Crown winner Seattle Slew to Yorkshire 'lowfat' pigs, people have been breeding animals and plants for desirable traits since prehistoric times. But there has been no easy way of telling which genes have been favored by the selective breeding. Until now.

By making use of the new technique of DNA microarrays ("chips"), a team of scientists lead by Ralph J. Greenspan at The Neurosciences Institute has discovered a way of solving the conundrum of identifying which genes have changed when breeding for a particular trait. In their study of two strains of the common fruit fly (Drosophila melanogaster), selected for differences in their response to gravity ("geotaxis"), they have found that the difference is due to small contributions from many genes, and they have identified several of the genes, two of which have human genetic counterparts.

"Behavior is not all genetic," Greenspan said. "but this one (geotaxis) has a strong genetic bias. This is the result of selecting for differences in responses to gravity in many generations of flies over many years."

The Institute's team used the new technology to sample approximately 40 percent of the fruit fly genome, which bears striking genetic similarity to those of humans. It is also quite easy to manipulate fruit fly genes in experiments.

"Every individual experiences a unique sequence of life events that plays off the unique combination of genes inherited from their parents. Understanding how genes influence us is one of the major challenges for the mass of genomic information that is becoming available. This particular example is very relevant for us humans, since our genetic biases are also likely due to small contributions from many genes."

In summary, the study is significant in three dimensions. It:

  1. Demonstrates a tangible and practical application of the great genome mapping project: DNA microarray "chip" technology (very small pieces of an organism's DNA placed and studied on a glass slide), that ultimately can be applied to discover and measure the activity of an organism's entire genome.

  2. Provides the first window into the genetic changes that occur during selective breeding for a particular trait.

  3. Strongly suggests that such changes are not due to a severe disruption in a single gene, but rather to many small changes and contributions from many genes. And, within each of the many genes, effective performance and change in one gene depend on the state of all the rest of the genes in the gene network.

The work presented in this week's Nature Genetics, a prestigious scientific journal, built upon one of the classical textbook experiments on selection for behavioral differences undertaken in the fruit fly in the 1950s and 1960s by leading behavior geneticist (and a co-author on the paper) Jerry Hirsch of the University of Illinois. At the time, Hirsch and his colleagues were able to derive certain fruit fly strains selected for opposing responses to gravity - one strain walks up in a maze, the other walks down. But they were not able to identify the genes that differed between them due to the fact that none of the genetic differences were very strong in themselves. Dan Toma, working with Greenspan at The Neurosciences Institute, and Kevin P. White at Yale University also participated in the work leading to these discoveries.



Ralph J. Greenspan, Ph.D., Scientist Dorothy and Lewis B. Cullman Senior Fellow in Experimental Neurobiology 858-626-2075;

Additional contacts:

Dr. Tim Tully, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY Tel: 516-367-8875; E-mail:

Dr. Steven J. de Belle, University of Nevada, Las Vegas, Las Vegas, NV Tel: 702 895 3271; E-mail:

The Neurosciences Institute focuses its research on the fundamental principles of functions of the brain, which is the single most complex organ in the known universe. The Institute is a small, privately funded, not-for-profit organization that utilizes an interdisciplinary approach to scientific investigation.

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