Published online 12 October 2004
Nucleic Acids Research, Vol. 32 No. 18 © Oxford University Press 2004; all rights reserved
‘Conserved hypothetical’ proteins: prioritization of targets for experimental study
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
* To whom correspondence should be addressed. Tel: +1 301 435 5913; Fax: +1 301 435 7794; Email: koonin{at}ncbi.nlm.nih.gov
Received August 18, 2004; Revised and Accepted September 22, 2004
Comparative genomics shows that a substantial fraction of the genes in sequenced genomes encodes ‘conserved hypothetical’ proteins, i.e. those that are found in organisms from several phylogenetic lineages but have not been functionally characterized. Here, we briefly discuss recent progress in functional characterization of prokaryotic ‘conserved hypothetical’ proteins and the possible criteria for prioritizing targets for experimental study. Based on these criteria, the chief one being wide phyletic spread, we offer two ‘top 10’ lists of highly attractive targets. The first list consists of proteins for which biochemical activity could be predicted with reasonable confidence but the biological function was predicted only in general terms, if at all (‘known unknowns’). The second list includes proteins for which there is no prediction of biochemical activity, even if, for some, general biological clues exist (‘unknown unknowns’). The experimental characterization of these and other ‘conserved hypothetical’ proteins is expected to reveal new, crucial aspects of microbial biology and could also lead to better functional prediction for medically relevant human homologs.
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