An ocean of genes
Speed-reading all the DNA in the sea--and the gut--could reveal worlds of unknown organisms
Nearly a decade ago, maverick geneticist J. Craig Venter proposed a speedy new way to decipher creatures' DNA codes. Though critics scoffed, saying his "shotgun" approach would never work, it yielded the first genome sequence of a free-living organism, a simple bacterium. Since then, the technique has unraveled the code of more-complex animals, including humans, and made deciphering the DNA from microbes practically routine.
Now, Venter's teams at private biotech institutes in Maryland are pushing sequencing into a new realm. They think they can use the technique to read the DNA of an entire ecosystem, or at least its microbial denizens, all at once. If their gambit works, they could quickly uncover the genetic code of hundreds, perhaps thousands, of known and unknown microbes in a pinch of soil, a tube of seawater, or even the human body. "It's a microbial fishing expedition, and we're trawling with a net that gets everything," says Venter. He and his colleagues plan to start with samples from the human digestive tract and the Sargasso Sea, a warm patch of ocean near Bermuda.
Scientists think the variety of still unknown microbes might surpass that of all known life. A single teaspoon of soil, says microbiologist Bob Goodman of the University of Wisconsin-Madison, can hold as many as 10,000 kinds of bacteria. Unknown microbes probably influence human disease, crop growth, and global climate and may provide valuable new antibiotics or industrial enzymes. But most can't be grown in the lab--the traditional way to study microbes.
Already, genetic tools have unearthed surprising microbial treasures. Edward DeLong of the Monterey Bay Aquarium Research Institute searched DNA collected from seawater for telltale genes and uncovered a new and important part of the sea's web of life: a microbe, abundant at the ocean's surface, that generates energy from sunlight, like a plant. But the new projects will go further. "The difference in what we're trying to do is just this brute force where we're going to go in and sequence everything that's there," says Karen Nelson of the Institute for Genomic Research, which is focusing on the gut study. An affiliated organization, the Institute for Biological Energy Alternatives, will tackle the seawater.
Quick study. Both projects will use the shotgun method Venter pioneered. They will extract DNA and break it up into many random pieces. A battery of high-speed sequencing machines will quickly determine the genetic letters in each piece. Then computers will put the jigsaw puzzle together, looking for overlaps at the ends of the pieces for clues to how they fit together in the full genome.
While this method works well for decoding the DNA of a single species, making sense of hundreds or even thousands of species in the same pot is another matter. The institutes' pilot studies showed that computers can tease out separate genomes from a mixture of known microbes. Putting the pieces together, however, could be difficult if many of the organisms are closely related, with similar DNA, as would be expected in samples of sea or gut. "The real hard part will be in trying to assemble genomes," says David Relman of Stanford University, who is collaborating on the gut study. But even if the technique can't distinguish all the individual genomes, it should still reveal whole groups of organisms or track genetic changes in an entire ecosystem.
Either way, the effort could unveil the countless invisible actors around us. Knowing the microbial gene profile of a healthy gut, for example, will help scientists learn how gut ecology changes when people get sick. And understanding the normal life in the ocean may let researchers detect population changes that give early warnings of pollution or other disturbances. "I think it will become the No. 1 way that environments are monitored in the future," says Venter. The naysayers don't bother him. After all, it wasn't so long ago that most people thought his shotgun approach wouldn't work for even one genome.
This story appears in the May 12, 2003 print edition of U.S. News & World Report.