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
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
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
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
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
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
worldwide," Rubin says.
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
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
"One of the big surprises over the last five years is how well conserved
these signaling pathways are," Rubin says. "Pathways discovered in
are doing the same things in vertebrates."
, 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
of the National Academy of Science.
Photo: Paul Fetters