Traditional microbiological nomenclature sometimes leads to misunderstandings, confusion, and other problems for microbiologists when, for example, they encounter the same gene within the type II secretion system through one or a few of its 20 or more different names-some of them based merely "on the phenotype it has in their bacterium," says Alan Collmer of Cornell University, Ithaca, N.Y. To address this issue more broadly, biologists launched the Gene Ontology (GO) project in 1998, focusing then on mouse, fruit fly, and yeast genes. However, microbiologists soon brought bacterial and other microbiological nomenclature challenges into this forum, and the fruits from some of their focused GO efforts can be found in the July issue of Trends in Microbiology (TiM).

"The gene ontology is a standardized set of terms, words, and phrases with well-defined meanings which the community has reviewed," says Brett M. Tyler of the Virginia Bioinformatics Institute (VBI), part of the Virginia Polytechnic Institute and State University in Blacksburg, Va. The terms represent specific biological processes, cellular components, and molecular functions, regardless of species. The annotations include an "evidence code" that tells what experiments support each annotation, thus giving biologists amore precise idea of what their colleagues mean.

Without the GO, genomics would face an even more difficult challenge to fulfill its promise of making gene comparisons between different species, Collmer says. "If somebody with another organism has made more progress in understanding the function of that gene, being able rapidly to connect with that function when analyzing your [microorganism's] genome is very powerful, but you can't do it based on the gene's name. The gene ontology provides a consensus universal language that operates across all organisms."

"We specifically ran into this problem in connection with pathogenesis," Collmer continues. Very different microbes interact with their respective plant hosts in similar fashion, regardless of whether the microorganism interacting with a particular host is a bacterium, a fungus, a nematode, or an oomycete. To describe these processes, the Plant-Associated Microbe Gene Ontology Consortium compiled more than 800 terms to describe such microbe-host interactions, according to one of the articles in the July TiM.

These efforts are expected to help when it comes to defining functions of different genes from sequences derived from mixed microbial populations in environmental samples. For example, the Human Microbiome Project plans to sequence metagenomes of five sites from the human body to learn more about how such microbial communities affect human health (see p. 451).

These improved GO terms will help humans program and then understand more fully the data sets that play such a vital role in tracking genomic analyses. "I can write a program that says ‘tell me all the genes in all microbes that have such and such a function,' and it will instantly give me the results," Tyler of VBI says. "Imagine doing a search on Google," he says, contrasting its fuzziness with the crispness of a search using carefully defined GO terms.

To further strengthen the GO, the Gene Ontology Reference Genome Project (www.geneontology.org/GO .refgenome.shtml) is developing reference annotations for 12 of the most important model organisms spanning the tree of life, from Escherichia coli to Arabidopsis and the zebrafish. That focused exercise "will make it far easier to automatically annotate new genomes," says Michelle Gwinn-Giglio of the University of Maryland School of Medicine in Baltimore.

GO is also being used extensively in microarray expression analysis and genome-wide association studies. The GO annotation repository, where GO annotation datasets are stored, contains hundreds of thousands of annotations for thousands of species. For microbiology, as well as biology generally, it is a powerful new tool. "I like to think of it as a universal biological language," says Gwinn-Giglio. "You could compare it to the Rosetta stone . . . but maybe that's a little over the top."

David Holzman
David Holzman is the Microbe Journal Highlights Editor.