Metagenomics

Advances in sequencing technology, which have made sequencing faster and less expensive, now provide the possibility of sequencing not just the genomes of individual species, but the genomes of entire communities of organisms. Metagenomics is an emerging field in which the genome sequences of an entire group of organisms that inhabit a common environment are sampled and determined.

Thus far, metagenomics has been applied largely to microbial communities. Traditionally, bacteria have been studied by growing and analyzing them in the laboratory. However, many bacteria cannot be cultured with the use of laboratory techniques. Metagenomics analyzes microbial communities by extracting DNA from the environment, determining its sequences, and reconstructing community composition and function based on those sequences. This technique allows the identification and genetic analysis of species that cannot be grown in the laboratory and have never been studied by traditional microbiological methods. The entire genomes of some dominant species have been reconstructed from environmental samples, providing scientists with a great deal of information on the biology of these microbes.

An early metagenomic study analyzed the microbial community found in acid drainage from a mine and determined that this community consisted of only a few dominant bacterial species. Another study, called the Global Ocean Sampling Expedition, followed the route of Darwin’s voyage on H.M.S. Beagle in the 1800s. Scientists collected water samples and used metagenomic methods to determine their microbial communities. In this study, scientists cataloged sequences for more than 6 million proteins, including more than 1700 new protein families.

Other metagenomic studies have examined the genes of bacteria that inhabit the human intestinal tract. These bacteria, along with those that inhabit the skin and other parts of the human body, are termed the human microbiome. The microbiome of a typical person includes over 100 trillion cells—more than 10 times the number of human cells—and contains 100 times as many genes as the human genome.

Research is demonstrating that the human microbiome plays an important role in human health. One study examined the gut microflora of obese and lean people. Two groups of bacteria are common in the human gut: Bacteroidetes and Firmicutes. Researchers discovered that obese people have relatively more Firmicutes than do lean people and that the proportion of Firmicutes decreases in obese people who lose weight on a low-calorie diet. These same results were observed in obese and lean mice. In an elegant experiment, researchers transferred bacteria from obese to lean mice. Lean mice that received bacteria from obese mice extracted more calories from their food and stored more fat, suggesting that gut microflora might play some role in obesity.

Ecological communities have traditionally been characterized on the basis of the species they contain. Metagenomics provides the possibility of characterizing communities on the basis of their component genes, an approach that has been termed gene-centric. A gene-centric approach leads to new questions: Are certain types of genes more common in some communities than in others? Are some genes essential for energy flow and nutrient recycling within a community? Because of the larger sizes of their genomes, eukaryotic communities have not yet been the focus of these approaches, but many researchers predict that they will be in the future.

CONCEPTS

Metagenomic studies examine the genomes of communities of organisms that inhabit a common environment. This approach has been applied to microbial communities and allows the composition and genetic makeup of a community to be determined without having to cultivate and isolate individual species. Metagenomic studies are sources of important new insights into microbial communities.