Scientists are sequencing the genomes of entire microbial communities in the hope of uncovering new genes and organisms that can create fuel, mine metals, or clean up superfund sites. Known as metagenomics, the field relies on studying bits of DNA from a variety of organisms that live in the same place. Thanks to ever-improving sequencing methods, the number of metagenome projects is growing, giving scientists myriad new genes to explore.
“This opens up a new way of looking at these organisms,” says Jim Bristow, director of the community sequencing program at the Department of Energy’s Joint Genome Institute, in Walnut Creek, CA. “We’ll probably discover lots of fundamental processes that we previously knew nothing about.”
Microorganisms make up an immensely important and often overlooked part of the environment. “They constitute the bulk of our biosphere and underpin all the nutrient cycles on our planet,” says Philip Hugenholtz, leader of the microbial ecology program at the Joint Genome Institute. “But our understanding of these systems is still rudimentary.” Microbiologists would like to better understand these communities, so they can co-opt useful genes or organisms, such as those that remove pollutants from soil, or better control microbial communities, such as those that live in our mouths or gut.
The standard way to identify and study the microorganisms living in a particular community is to grow them in a lab, but this is only possible with about 1 percent of microbes. However, in the past two years, faster and cheaper gene-sequencing methods have offered microbiologists a new tool with which to study the other 99 percent. Scientists can extract the DNA from, say, a drop of seawater or a sample of sludge from a sewage-treatment plant and then sequence that DNA, deriving genomic clues to all the organisms living in that environment.
Assembling the random fragments of DNA generated during sequencing can be a challenge–even impossible in some cases. Hugenholtz likens the process to trying to put together one thousand jigsaw puzzles from a single box that holds only a few pieces from each puzzle. So rather than fully assembling these genomic puzzles, scientists try to understand the individual pieces, or genes. Identifying the genes that allow the microbes in the termite gut to digest wood, for example, could lead to better biofuels. Converting cellulose in trees and grasses into the simple sugars that can be fermented into ethanol is a very energy-intensive process. “If we had better enzymatic machinery to do that, we might be better able to make sugars into ethanol,” Bristow says. “Termites are the world’s best bioconverters.”
Researchers at the Joint Genome Institute, which sequenced some of the human genome and is now largely devoted to metagenomics, have just finished sequencing the microbial community living in the termite gut. They have already identified a number of novel cellulases–the enzymes that break down cellulose into sugar–and are now looking at the guts of other insects that digest wood, such as an anaerobic population that eats poplar chips. The end result will be “basically a giant parts list that synthetic biologists can put together to make an ideal energy-producing organism,” says Hugenholtz.
Several other projects–from whale carcasses to wastewater sludge–are under way or already complete, promising a huge volume of novel genetic data. A recent project at the University of California, Berkeley, for example, identified three new organisms living in the highly acidic environment of abandoned mines. (Bacteria covering the floors of these mines convert iron into acid, which can then pollute nearby streams.) “They are close to the size of viruses and may be the smallest organisms ever discovered,” says Brett Baker, a research scientist at UC Berkeley, who worked on the project with Jill Banfield, also at UC Berkeley. These organisms may give clues to other life forms adapted to extreme environments, such as Mars.
The next hurdle in metagenomics will be trying to find the function of many of the newly identified genes: unlike cellulases in termites, most genes have little structural similarity to genes of well-studied organisms, making it difficult to infer their function. In a sample of water from the Sargasso Sea collected by genomics pioneer Craig Venter, the two most common and likely most important gene families are totally unique: scientists have no idea what they do. “In some ways, it’s crude to focus on enormous mountains in the genomic landscape,” says Hugenholtz. “But it does immediately draw attention to interesting avenues to pursue.” Structural studies are now under way to try to figure out these proteins’ function.
Metagenomics projects may eventually be able to shed light on these unknown genes. “We can look at representations of genes of unknown function in similar environments, compare them to environments that lack a particular function, and then triangulate,” says Bristow. And metagenomic signatures could one day be used as a fingerprint to identify certain environments, he adds. They “could be used as a way of identifying places you might want to drill for oil or look for minerals or contamination of some kind,” he says. “Just seeing the genes might tell you what’s happening there.”