September 01, 1998
Rapid Screening Technique Advances Efforts to Determine Gene Function
Gerald M. Rubin and colleagues can now probe the expression patterns of 96 Drosophila genes at a time. Their technique should speed the identification of novel genes involved in fruit fly development.
A rapid technique for tracking the expression of genes in the fruit
fly Drosophila has identified hundreds of previously unknown
genes that are likely to play a role in the orderly growth and
development of animals ranging in complexity from insects to
humans.
Researchers have long studied gene expression by examining one gene
at a time. But developmental biologists led by Gerald M. Rubin and
Corey S. Goodman of the Howard Hughes Medical Institute at the
University of California, Berkeley, developed a technique that speeds
the process by probing the expression patterns of 96 genes at a time.
"We can very rapidly screen large numbers of genes for a particular
expression pattern," Rubin says. Expression patterns indicate when a
gene is turned on and thus directing the production of a specific
protein.
“Part of what we are doing is creating a resource for all who study Drosophila worldwide.”
Gerald M. Rubin
In an article in the August 18, 1998, issue of Proceedings of the
National Academy of Sciences, the HHMI research team mapped gene
expression for 2,518 segments of DNA from fruit fly embryos. The genes
included 917 whose pattern of expression changes as the embryo grows,
indicating that the genes may play a role in directing fruit fly
development. When the researchers sequenced 1,001 of the gene segments
and compared the sequences with those of known genes, they found that
811 represented new genes. The rapid identification of so many genes in
a long-studied organism reflects the strength of the new approach.
The researchers identified so many previously missed developmental
genes in part because the new method overcomes some of the
disadvantages of older techniques that relied on introducing mutations
into an animal's genome to "knock out" one of its genes and then see
what changes occur in the organism. Rubin has estimated that for about
two-thirds of Drosophila genes, defects resulting from such
experiments yield no apparent changes in the fly, often because other
genes can fulfill that same function as the altered gene. Other genetic
manipulations are lethal early in development, eliminating the
possibility of observing any changes at all.
The HHMI team designed their experiments to favor discovering genes
that play a role in signaling that occurs between cells. Such signaling
is the guiding force in stimulating processes that shape the
development of an organism from a single fertilized egg to an adult.
Although the researchers focused on developmental genes, the lab
protocol can be adapted for rapid screening of all kinds of genes,
Rubin explains.
The data from this study can be viewed on the World Wide Web as part
of the Berkeley Drosophila Genome Project, sponsored by the
Department of Energy and the National Institutes of Health. "Part of
what we are doing is creating a resource for all who study
Drosophila worldwide," Rubin says.
Drosophila studies have a history stretching back nine
decades to Thomas Hunt Morgan's seminal experiments mapping genes to
specific chromosomes in the cell nucleus. As was the case in Morgan's
day, fundamental principles observed in Drosophila operate in
other, less easily studied organisms. In recent decades, developmental
biologists have identified sets of genes that trigger production of
signaling proteins that guide the orderly development of body segments
and establish the organism's central axis.
"One of the big surprises over the last five years is how well
conserved these signaling pathways are," Rubin says. "Pathways
discovered in Drosophila are doing the same things in
vertebrates."
Norbert
Perrimon, an HHMI investigator at Harvard Medical School, says that
"studying the fly is a way to dissect signaling pathways that have been
conserved through evolution and that are relevant to human physiology
and disease." He adds that genes that play a role in normal growth in
the fly also have been shown to be abnormal in some human birth defects
and cancers. Perrimon's commentary on Rubin's and Goodman's research
also appears in the August 18, 1998, issue of Proceedings of the
National Academy of Science.
Photo: Paul Fetters
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