乳糖操纵子Lactose Operonfor graduate students牛登科生命科学学院2010年10月Lactose OperonStructural geneslac z, lac y, & lac aPromoterPolycistronic mRNARegulatory geneRepressorOperatorOperonInducer - lactoseiOperonRegulatoryGenepozyaDNAm-RNA-GalactosidasePermeaseTransacetylaseProteinLactose OperonInducer - lactoseAbsenceActive repressorNo expressionipozyaNo lac mRNAAbsence of lactoseActiveipozya-GalactosidasePermeaseTransacetylasePresence of lactoseInactivePresenceInactivation of repressorExpressionNegative controlIs the story complete?These two pages are copied from the PPT of an American teacher. Has your textbook told you something more?If no, are you satisfied with this theory?No lactose, no genes transcribed, no proteins produced, and then nothing to transport lactose into the cell.A dead cycleBasal transcriptionThe repressor could not entirely repress the genes. In absence of lactose, there is a low level of leaky gene expression of lactose operon genes.The negative control of lactose operon is not yes or no, but more or less. In fact, in eukaryotes, there are also many genes that are transcribed and translated, at low levels, in the cells that obviously do not need them. And the reason for this is not clear, awaiting for you to discover.Do you still have any question?Why operon?Operons contain genes belonging to the same functional pathway in order to guarantee them a similar expression level. About half of the protein-coding genes are organized in operons.However, prokaryotic genomes are rather unstable and only 525% of genes belong to strings shared by at least two distantly related species. The biological significance and mechanism(s) of operon formation are still under debate. At least seven different models have been proposed for operon formation.For details, see Res. Microbiol. 160: 502-512, 2009.More questions?Why negative control?That is, is there any trouble if the lactose operon genes are constitutively expressed?Waste of amino acids in useless proteinReally?Consider a workshop, e.g. frozen sucker, popsicle. If the products could not be sold out, what is the cost? Waste of water?The cost is associated with the process of making the lac gene products. See Genetics 178: 16531660, 2008.The cost of wasteful protein expressionCells growing in rich media have higher ribosome content than cells growing in poor media. Thus, when cells are shifted from rich to poor media they have an excess of ribosomes and can absorb the cost of excess translation.On shift from poor to rich media, cells have insufficient ribosomes and exhibit the cost.Since the costs are manifest only in some transitions, it is not change alone but a deficit of some specific cellular component (ribosomes are the likely candidate) that exacerbates costs.Shachrai I, Zaslaver A, Alon U, Dekel E: Cost of Unneeded Proteins in E. coli Is Reduced after Several Generations in Exponential Growth. Mol Cell 2010, 38(5):758-767.Stoebel DM, Dykhuizen DE: Waste and yet want not. Mol Cell 2010, 38(5):625-626.Why operon in C. elegan revealedWe find that transcriptional resources are initially limiting during recovery and that recovering animals are highly sensitive to any additional decrease in transcriptional resources. We provide evidence that operons become advantageous because, by clustering growth genes into operons, fewer promoters compete for the limited transcriptional machinery, effectively increasing the concentration of transcriptional resources and accelerating recovery. From Zaslaver A, Baugh LR, Sternberg PW: Metazoan operons accelerate recovery from growth-arrested states. Cell 2011, 145(6):981-992.And something else?Left for you to discoverAnd Eames M, Kortemme T: Cost-Benefit Tradeoffs in Engineered lac Operons. Science 2012, 336(6083):911-915.Plata G, Gottesman ME, Vitkup D: The rate of the molecular clock and the cost of gratuitous protein synthesis. Genome Biol 2010, 11(9):R98.