'Conserved hypothetical' proteins: prioritization of targets for experimental study.
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.
Galperin
Michael Y
MY
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Koonin
Eugene V
EV
D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D019295:Computational Biology; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D023281:Genomics; D006801:Humans; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D005656:Fungal Proteins; D011506:Proteins