A tiny transparent worm has enabled the first complete description of the biochemical steps leading from a genetic mutation to a change in behavior, UT Southwestern Medical Center at Dallas investigators have reported.

   The understanding of the connection between genes and behavior at the molecular level is a major goal of neurobiology.

   "A question we want to answer in looking at the human genome is what controls behavior," said Dr. Leon Avery, associate professor of molecular biology at UT Southwestern and senior author of the paper. "I believe a lot of the genetics of human behavior will be understandable in molecular terms through a change in a single ion channel or single receptor molecule."

   The report appeared in the December 24th issue of Science.

   The researchers studied a worm called a c. elegans that had a mutation that affected its feeding behavior. They showed that the mutation in the gene exp-2 caused an abnormality in a potassium channel so that it remained open rather than opening and closing normally. This alteration prevented opening of the pharynx, the muscle used to eat.

   The opening of the potassium channel, called EXP-2, causes muscle relaxation. Normally the muscle relaxes a fifth of a second after contraction of the muscle. In the mutant worms, it relaxed in a 20th of a second after the contraction. This meant the muscle never contracted or opened all the way. The worms could not eat much because they could not take in adequate food.

   "A good way to imagine this is that the pharyngeal muscle is like a pump, pumping food into the worm," Avery said. "It works very much like a human heart. If a heart pumps too fast, it can't really pump any blood before it starts to relax again."

   Because the scientists were able to describe the biophysical, electrophysiological and behavioral effects of this mutation, they now know every step in the causal chain linking a mutation to altered feeding behavior in c. elegans. The researchers believe that studying such changes in molecules eventually may answer behavioral questions right down to why some people are cheerful and others are grumpy.

   The scientists also concluded from studying the worms' EXP-2 channel, which is related to the human potassium channel HERG, that these similarly functioning channels, although different in structure and sequence, apparently evolved to fill the same needs in different animals. The researchers now will try to determine if modifying the behavior of the EXP-2 channel also changes the worms' feeding behavior.

   The lead author of the study, Dr. M. Wayne Davis, recently earned his doctorate at UT Southwestern and is now at the University of Utah. Dr. Richard Fleischhauer, postdoctoral fellow, and Dr. Rolf Joho, associate professor of cell biology, both in the UT Southwestern Center for Basic Neuroscience, and Dr. Joseph Dent, assistant professor of biology at McGill University, Montreal, collaborated on the study.