Beetlejuice genes now in biotechnicolor.

Beetlejuice genes now in biotechnicolor

"Beetlejuice" may be passe by Hollywood standards; the popular comedy film has been gone from theaters for months. But Beetlejuice II is coming soon -- not to local theaters this time, but to a biotechnology lab near you.

Researchers working with Caribbean click beetles have isolated the genes coding for bioluminescence from the juices of these glow-in-the-dark bugs. Having inserted this DNA into bacteria, they have developed a multicolored system of "reporter genes" they say will allow scientists to measure simultaneously the activity of several otherwise invisible, spliced genes in cell cultures. Until now, reporter gene systems -- which indicate when a gene is turned on -- have necessitated much more complicated procedures and could only track one spliced gene at a time.

Keith V. Wood and William D. McElroy of the University of California, San Diego, and their colleagues started with the Jamaican click beetle, Pyrophorus plagiophthalamus, a distant relative of the firefly. Like fireflies (which are beetles, not flies), click beetles contain light-generating organs in their abdomens. But unlike fireflies, click beetles glow in a variety of colors.

All bioluminescent beetles, including fireflies, produce colored light by enzymatically cleaving molecules of an identical protein substrate, called luciferin. Different enzymes, known collectively as luciferases, cut luciferin in different places, producing various colors of light. Wood and his co-workers cloned the genes for four click-beetle luciferases and inserted them into the common intestinal bacteria Escherichia coli. When they bathed the bacteria in luciferin, characteristic colors appeared within about 30 seconds, indicating gene activity.

By linking various luciferase genes to other genes of interest spliced into cells, scientists can now measure the relative activity rates of multiple genes in cells over time. The one-step process (scientists simply add luciferin and measure light intensity for each color) is far easier and more than 100 times more sensitive than current methods, the researchers report in the May 12 SCIENCE. In the standard reporter gene system commonly used today, scientists spend hours separating and measuring enzymatically altered, radioactively labeled substrates.

"A real revolution has come from our ability to look at how genes work," says Wood, who first basked in the glow of scientific luminosity in 1986 when he and co-workers made the world's first glow-in-the-dark tobacco plants by splicing into the plants a luciferase gene from a firefly. "We've gotten to the point now where we'd like to look at how more than one gene works at a time. This supplies a marvelous technology for allowing us to go that next step and look at the coordination between genes."

The researchers have identified minor variations in luciferase genetic sequences that account for the different colors -- a finding that suggests they may soon be able to add to their Pyrophorus palette. Soon, says Wood, "we may be able to do things with color that we haven't yet seen in natural systems."