Primer on Microbial Genomics cont'd
Annotation and Analysis
After a microbe's complete genomic sequence is determined, these data are analyzed, or annotated, to identify all the potential genes and to get clues about possible gene functions.
One of the surprises emerging from the study of a number of microbial sequences is the presence of genetic segments containing not just single genes but entire blocks of multiple genes that appear to have been acquired intact during evolution from other microbes in very distant parts of the tree of life. The bacterium T. maritima is hypothesized to have acquired a quarter of its genome through this process, which is termed "lateral gene transfer." These findings present exciting challenges to our understanding of how microbial species live and evolve.
The availability of complete genomes has opened up the entirely new field of comparative genomics, which is allowing researchers to identify genes that are similar across species. Comparative genomics is providing clues into the functions of genes and how genomes change over time. Comparative studies also are having a profound impact on the ability to discover novel genes and biochemical pathways. To interpret genome sequences, scientists first compare them to other entries in DNA sequence databases. Astonishingly, some one-third of genes discovered in newly sequenced genomes do not have database matches and, therefore, no easily identifiable functions.
These data demonstrate how little is known about microbial species, and, as each completed genome sequence reveals novel sets of genes, many of them may be identified as unique to a particular species or to particular functions present in some strains of microbes but lacking in others. These newly identified genes represent exciting opportunities for future basic research and potential sources of biological resources to be explored for future use. The usefulness of comparative techniques improves dramatically as more genomes become available, but better methods are needed to expand the types of analyses that can be performed.
While the DOE MGP focuses primarily on environmental, energy, and biotechnological areas, there may be spinoff applications in medicine as well. Potential biomedical benefits from comparative genomics studies include insights into the specialized, shared systems used by disease-causing organisms (pathogens) to disable or destroy human cells. Comparing these genomic data with those of other microbes may help scientists understand a diverse range of pathogens that have remarkably similar methods for infiltrating organisms with protein-coding genes capable of sneaking past human defense systems. These protein structures may provide ideal targets for developing completely new types of antibiotics.
Researchers have only scratched the surface of microbial biodiversity. Given the pervasiveness of microbes in all environments as well as their ancient evolutionary history, one can expect to find a vast repertoire of useful functions in the microbial world that could be applied to solving challenges in the human world.
Text from Human Genome Program, U.S. Department of Energy, Microbial Genome Program Report, February 2000.