A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations - PubMed (original) (raw)
B Teusink, D Broadhurst, N Zhang, A Hayes, M C Walsh, J A Berden, K M Brindle, D B Kell, J J Rowland, H V Westerhoff, K van Dam, S G Oliver
Affiliations
- PMID: 11135551
- DOI: 10.1038/83496
A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations
L M Raamsdonk et al. Nat Biotechnol. 2001 Jan.
Abstract
A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent, " that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing "metabolic snapshots," can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY-an abbreviation for functional analysis by co-responses in yeast.
Similar articles
- Snapshots of metabolic phenotypes.
Alfred J. Alfred J. Nat Rev Genet. 2001 Mar;2(3):162. doi: 10.1038/35056003. Nat Rev Genet. 2001. PMID: 11256066 No abstract available. - Functional genomics: lessons from yeast.
Oliver SG. Oliver SG. Philos Trans R Soc Lond B Biol Sci. 2002 Jan 29;357(1417):17-23. doi: 10.1098/rstb.2001.1049. Philos Trans R Soc Lond B Biol Sci. 2002. PMID: 11839178 Free PMC article. - Large-scale mutagenesis and functional genomics in yeast.
Que QQ, Winzeler EA. Que QQ, et al. Funct Integr Genomics. 2002 Sep;2(4-5):193-8. doi: 10.1007/s10142-002-0057-3. Epub 2002 May 9. Funct Integr Genomics. 2002. PMID: 12192592 Review. - High-dimensional and large-scale phenotyping of yeast mutants.
Ohya Y, Sese J, Yukawa M, Sano F, Nakatani Y, Saito TL, Saka A, Fukuda T, Ishihara S, Oka S, Suzuki G, Watanabe M, Hirata A, Ohtani M, Sawai H, Fraysse N, Latgé JP, François JM, Aebi M, Tanaka S, Muramatsu S, Araki H, Sonoike K, Nogami S, Morishita S. Ohya Y, et al. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19015-20. doi: 10.1073/pnas.0509436102. Epub 2005 Dec 19. Proc Natl Acad Sci U S A. 2005. PMID: 16365294 Free PMC article. - Metabolite profiling of fungi and yeast: from phenotype to metabolome by MS and informatics.
Smedsgaard J, Nielsen J. Smedsgaard J, et al. J Exp Bot. 2005 Jan;56(410):273-86. doi: 10.1093/jxb/eri068. Epub 2004 Dec 23. J Exp Bot. 2005. PMID: 15618299 Review.
Cited by
- The metabolic domestication syndrome of budding yeast.
Tengölics R, Szappanos B, Mülleder M, Kalapis D, Grézal G, Sajben C, Agostini F, Mokochinski JB, Bálint B, Nagy LG, Ralser M, Papp B. Tengölics R, et al. Proc Natl Acad Sci U S A. 2024 Mar 12;121(11):e2313354121. doi: 10.1073/pnas.2313354121. Epub 2024 Mar 8. Proc Natl Acad Sci U S A. 2024. PMID: 38457520 Free PMC article. - Proteomics and Metabolomics Analysis Reveal the Regulation Mechanism of Linoleate Isomerase Activity and Function in Propionibacterium acnes.
Liu Y, Chen Y, Yue X, Liu Y, Ning J, Li L, Wu J, Luo X, Zhang S. Liu Y, et al. ACS Omega. 2023 Dec 18;9(1):1643-1655. doi: 10.1021/acsomega.3c08243. eCollection 2024 Jan 9. ACS Omega. 2023. PMID: 38222669 Free PMC article. - Quantitative LC-MS study of compounds found predictive of COVID-19 severity and outcome.
Roberts I, Wright Muelas M, Taylor JM, Davison AS, Winder CL, Goodacre R, Kell DB. Roberts I, et al. Metabolomics. 2023 Oct 18;19(11):87. doi: 10.1007/s11306-023-02048-0. Metabolomics. 2023. PMID: 37853293 Free PMC article. - Are allometric model parameters of aboveground biomass for trees phylogenetically constrained?
Huang XZ, Li FB, Wang ZX, Jin Y, Qian H. Huang XZ, et al. Plant Divers. 2022 Dec 2;45(2):229-233. doi: 10.1016/j.pld.2022.11.005. eCollection 2023 Mar. Plant Divers. 2022. PMID: 37069928 Free PMC article. - Liver metabolomic characteristics in three different rat models of deficiency based on ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.
Xingyao HU, Hongning L, Xiaojun Y, Zhong C, Liu FU, Ge L, Xuan C, Guangbin S. Xingyao HU, et al. J Tradit Chin Med. 2023 Apr;43(2):274-285. doi: 10.19852/j.cnki.jtcm.20230201.001. J Tradit Chin Med. 2023. PMID: 36994515 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous