A team of scientists from four universities has isolated the gene that controls most or all sexual behavior in male fruit flies. Their research is the first to pinpoint a single gene that works in the brain to govern nearly all aspects of a complex behavior in adult animals.
The scientists from Stanford, the University of Texas Southwestern Medical Center at Dallas, Brandeis University and Oregon State University report their findings in the Dec. 13 issue of the journal Cell.
The gene fru governs the fly's courtship and mating ritual, including its courting song. Here a male with a normal copy of the gene lifts one wing and vibrates it in a rhythmic song, as recorded on an oscilloscope below the drawing. Males with a slight alteration, or mutation, of the fru gene have subtle changes in their songs. With severe mutations, the flies do not sing a note, though they can flick their wings and can use them to fly. (courtesy: Jeffrey Hall, Brandeis University)
Geneticists have known for years that the gene, called fruitless and nicknamed fru, influences sexual orientation in the fly Drosophila melanogaster. Male flies with some mutations in the fru gene become bisexual -- they cannot tell other males from female flies when courting. With this research, the team of geneticists cloned and isolated the fru gene, and showed that it controls much more than the male's choice of partners.
They showed that the fru gene is:
- A master gene that controls not only sexual orientation but all, or nearly all, the steps in the male fly's elaborate courtship ritual -- from its first interest in a female through its rhythmic courting song, to its attempts to mate.
- Part of a group of genes that work together to govern all aspects of sex in these flies, including development of male and female organs.
- At work in a very small fraction of the cells in the fly's brain. The properties of the fru gene's target neurons suggest that they carry out command-and-control functions to set up and coordinate the complex events of male courtship and copulation.
"There has been speculation recently that no single gene could control a complex behavior. This work shows that a gene can do so -- at least in fruit flies," said Stanford biologist Bruce Baker, one of the four principal investigators of the study.
The gene fru governs the fly's courtship and mating ritual, including the male fly's ability to recognize a female. Males with a normal copy of the gene, at right, pursue only females. Males with an alteration, or mutation, of the fru gene, at left, court both sexes, and sometimes form chains with each male courting the one in front of it. (courtesy: Jeffrey Hall, Brandeis University)
The lead author on the Cell article is Lisa Ryner, a research associate in Baker's lab at Stanford. The principal investigators on the National Institutes of Health-sponsored study are Baker, professor of biological sciences at Stanford and an expert on the molecular genetics of sexual differentiation; Steven Wasserman, associate professor of molecular biology and oncology at UT Southwestern, an expert on the molecular genetics of fertility; Jeffrey Hall, professor of biology at Brandeis University and an expert on genetics and fly sexual behavior; and Barbara Taylor, assistant professor of biology at Oregon State University and an expert on genetics and the fly's nervous system.
Co-authors include postdoctoral research fellow Stephen F. Goodwin and research associate Adriana Villella of Brandeis; postdoctoral fellow Anuranjan Anand of Stanford; and Diego H. Castrillon, formerly an M.D./Ph.D. student at UT Southwestern, now a resident in pathology at Brigham and Women's Hospital and Harvard University Medical School.
"These findings on fru provide a starting point for a whole host of other studies, to learn how sexual behavior and sexual orientation are specified by genes and controlled by the nervous system," Wasserman said.
"Our data so far suggest that fru is involved in interactions between a handful of specific brain cells that in some way direct the various steps of male courtship behavior and copulation," Taylor said. "This is an important tool -- here we have a gene that allows us to extract some behavioral element and then go into the nervous system and see how it is organized."
"This is a spectacular example of the value of open exchange at scientific conferences," said Wasserman. The labs joined forces at an international meeting when he and Baker realized that each of their groups had half the essential information needed to clone and understand the role of the fru gene. "We had a map, and they knew where the crucial point in the map was," Wasserman said. "To go on and understand how the gene works called for the skills of the other two labs as well."
Important evidence that fru is the gene normally controlling most male sex behavior in the fruit fly comes from the fact that it fits in a hierarchy of genes that governs all other aspects of sex as well. In Drosophila males, "doublesex" (dsx) commands the development of male sex organs and other male characteristics, while "fruitless" (fru) commands male sexual behavior. Genes higher up in the family tree act to turn off dsx and fru so that female flies do not exhibit male sex organs or male behavior. (courtesy: Bruce Baker, Stanford University) Could human sexual behavior be commanded by a single gene? So far, no gene similar to fru has been found in humans or other animals. But geneticists have been studying fruit flies for more than 80 years to learn how genes instruct the building of the fly's body and the function of its cells, and insights from that work have already helped explain how the human body develops.
"In any complex organism, brain formation and function must be controlled in part by genes," Hall said. "The question is not whether but how do the actions of a given gene influence some interesting aspect of behavior."
However, he said, "Even if a gene of this sort could be identified in humans, that does not mean it would solely 'determine' behavior. By definition, those actions are also influenced by upbringing and environment -- even in flies."