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'Conserved hypothetical' proteins: prioritization of targets for experimental study
Open accessAbstract
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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Cites
Detecting Protein Function and Protein-Protein Interactions from Genome Sequences
Marcotte, E. M., Pellegrini, M., Ng, H.-L., Rice, D. W., Yeates, T. O., & Eisenberg, D. (1999) · Science · doi:10.1126/science.285.5428.751 · Cited by 1,670
Comparative genomics, minimal gene-sets and the last universal common ancestor
Koonin, E. V. (2003) · Nature Reviews Microbiology · doi:10.1038/nrmicro751 · Cited by 661
Cited by
Orthologs, Paralogs, and Evolutionary Genomics
Koonin, E. V. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.073003.114725 · Cited by 1,323
The cyanobacterial genome core and the origin of photosynthesis
Mulkidjanian, A. Y., Koonin, E. V., Makarova, K. S., Mekhedov, S. L., Sorokin, A., Wolf, Y. I., Dufresne, A., Partensky, F., Burd, H., Kaznadzey, D., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605709103 · Cited by 324
Self-citationAn annotated catalogue of salivary gland transcripts in the adult female mosquito, Ædes ægypti*
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Bachovchin, D. A., Ji, T., Li, W., Simon, G. M., Blankman, J. L., Adibekian, A., Hoover, H., Niessen, S., & Cravatt, B. F. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1011663107 · Cited by 274
Valdés-Mas, R., Leshem, A., Zheng, D., Cohen, Y., Kern, L., Zmora, N., He, Y., Katina, C., Eliyahu-Miller, S., Yosef-Hevroni, T., et al. (2025) · Cell · doi:10.1016/j.cell.2024.12.016 · Cited by 89
Metadata
- Authors
- Galperin, M. Y.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-10-11
- Volume
- 32
- Issue
- 18
- Pages
- 5452-5463
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2103601429
- Cited by
- 418
- References
- 2
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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