Like genomics, metagenomics is both a set of research techniques, comprising many related approaches and methods, and a research field. In Greek, meta means “transcendent.” In its approach and methods, metagenomics overcomes the twin problems of the unculturability and genomic diversity of most microbes, the biggest roadblocks to advancement in clinical and environmental microbiology. Meta in the first sense means that this new science seeks to understand biology at the aggregate level, transcending the individual organism to focus on the genes in the community and how genes might influence each other’s activities in serving collective functions. In the second sense, meta also recognizes the need to develop computational methods that maximize understanding of the genetic composition and activities of communities so complex that they can only be sampled, never completely characterized.
Metagenomics, still a very new science, has already produced a wealth of knowledge about the uncultured microbial world because of its radically new ways of doing microbiology. All metagenomics studies take the same first step: DNA is extracted directly from all the microbes living in a particular environment. The mixed sample of DNA can then be analyzed directly, or cloned into a form maintainable in laboratory bacteria, creating a library that contains the genomes of all the microbes found in that environment (see Box S-1). The library can then be studied in several ways, based primarily either on analyzing the nucleotide sequence of the cloned DNA or on determining what the cloned genes can do when they are expressed as proteins. It is important to recognize that the library is not organized into neat volumes, each containing the genome of one community member. Instead,
Clones and Libraries
The word clone can have several different meanings in biology. In the context of this report, the word is used to describe a process whereby fragments of DNA isolated from a microbial community are inserted—or cloned—into circular pieces of DNA called plasmids. Laboratory bacteria can be manipulated to take up all the plasmids; when the bacteria subsequently divide, they replicate the plasmid along with their genomic DNA. When a large collection of plasmids containing all the DNA fragments from a given community is cloned into a bacterial culture, the resultant collection of bacteria is called a library—a living repository of all of the DNA from a microbial community.