Conserved 'hypothetical' proteins: new hints and new puzzles.
Conserved hypothetical proteins, i.e. conserved proteins whose functions are still unknown, pose a challenge not just to functional genomics but also to general biology. For many conserved proteins, computational analysis provides only a general prediction of biochemical function; their exact biological functions have to be established through direct experimentation. In the few cases when this has been accomplished, the results were remarkable, revealing the deoxyxylulose pathway and a new essential enzyme, the ITP pyrophosphatase. Comparative genome analysis is also instrumental in illuminating unsolved problems in biology, e.g. the mechanism of FtsZ-independent cell division in Chlamydia, Ureaplasma and Aeropyrum or the role of uncharacterized conserved domains in signal transduction.
Galperin
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National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. galperin@ncbi.nlm.nih.gov