Gene regulation is a fundamental mechanism that allows for the variation in gene expression under different circumstances. This process is crucial in conserving energy by ensuring that proteins are synthesized only when necessary. Bacterial chromosomes, such as those found in Escherichia coli (E. coli), typically contain approximately 4400 genes, with some exhibiting constant expression levels across various conditions. These genes, known as constitutive genes, are responsible for encoding proteins essential for bacteria’s survival. However, the majority of bacterial genes are carefully regulated. The regulation of gene expression ensures that the products they encode are synthesized at the right times (temporal regulation), and in the correct amounts (quantitative regulation) at the right place within the cell (spatial regulation). This dynamic control of gene expression enables bacteria to adapt to changing environments and effectively carry out their biological functions.
Multiple-choice questions
Questions for Discussion
- E. coli primarily lives in the mucus layer of the mammalian intestinal tract. It quickly establishes itself in the intestines within 48 hours after birth. The presence of lactose in the gut during this time may give E. coli an advantage in colonizing this environment. However, lactose becomes scarce after the weaning period, except for humans who continue to consume dairy products. Since lactose is absent in adulthood for most mammals, the selective pressure to maintain the lac operon in the E. coli genome does not exist for long periods. Despite this, E. coli still retains the lac operon in its genome. Discuss various reasons for this.
- The discovery of riboswitches suggests that they are efficient in controlling metabolic pathways and can adapt to changes in the environment. So, why did regulatory mechanisms involving proteins were involved
- Discuss the molecular and cellular processes that enable the evolution of attenuation in the regulation of amino acid biosynthesis in bacteria.
- Do you think attenuation can be used to control carbohydrate synthesis? Why or why not?
- Secondary structures, as well as the bending and looping of DNA, play a crucial role in regulating operons. Furthermore, extensive research has indicated that modifications to DNA bases can impact chromosome structure, thus influencing gene regulation. Explore the impact of DNA methylation on the control of different operons mentioned in this chapter.
Further Reading
3.1 Transcriptional Control
Blumenthal, T., Davis, P., & Garrido-Lecca, A. (2015). Operon and non-operon gene clusters in the C. elegans genome. WormBook: The Online Review of C. Elegans Biology, 1–20. https://doi.org/10.1895/wormbook.1.175.1
Busby, S. J. W. (2019). Transcription activation in bacteria: Ancient and modern. Microbiology (Reading, England), 165(4), 386–395. https://doi.org/10.1099/mic.0.000783
English, M. A., Gayet, R. V., & Collins, J. J. (2021). Designing Biological Circuits: Synthetic Biology Within the Operon Model and Beyond. Annual Review of Biochemistry, 90, 221–244. https://doi.org/10.1146/annurev-biochem-013118-111914
Miller, J., and Reznikoff, W., eds. (1980). The Operon, 2nd ed. Woodbury, NY: Cold Spring Harbor Laboratory Press. Sanganeria, T., & Bordoni, B. (2023). Genetics, Inducible Operon. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK564361/
3.2. Enzyme Adaptation
Femerling, G., Gama-Castro, S., Lara, P., Ledezma-Tejeida, D., Tierrafría, V. H., Muñiz-King, A. N., de Mets, F., & Brinsmade, S. R. (2020). Who’s in control? Regulation of metabolism and pathogenesis in space and time. Current Opinion in Microbiology, 55, 88–96. https://doi.org/10.1016/j.mib.2020.05.009 Jacob, F., and Monod, J. (1961). Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3, 3 1 8-389.
3.3 Lac operon
Beckwith, J. (1978). lac: the genetic system. In Miller, J. H. and Reznikoff, W., eds. The Operon. New York: Cold Spring Harbor Laboratory, pp. 1 1-30
Friedman, A. M., Fischmann, T. O., & Steitz, T. A. (1995). Crystal structure of lac repressor core tetramer and its implications for DNA looping. Science (New York, N.Y.), 268(5218), 1721–1727. https://doi.org/10.1126/science.7792597
Gilbert, W., & Müller-Hill, B. (1966). Isolation of the lac repressor. Proceedings of the National Academy of Sciences of the United States of America, 56(6), 1891–1898. https://doi.org/10.1073/pnas.56.6.1891
Gilbert, W., & Müller-Hill, B. (1967). The lac operator is DNA. Proceedings of the National Academy of Sciences of the United States of America, 58(6), 2415–2421. https://doi.org/10.1073/pnas.58.6.2415
Görke, B., & Stülke, J. (2008). Carbon catabolite repression in bacteria: Many ways to make the most out of nutrients. Nature Reviews. Microbiology, 6(8), 613–624. https://doi.org/10.1038/nrmicro1932
Lewis, M. (2013). Allostery and the lac Operon. Journal of Molecular Biology, 425(13), 2309–2316. https://doi.org/10.1016/j.jmb.2013.03.003
Lewis, M., Chang, G., Horton, N. C., Kercher, M. A., Pace, H. C., Schumacher, M. A., Brennan, R. G., & Lu, P. (1996). Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science (New York, N.Y.), 271(5253), 1247–1254. https://doi.org/10.1126/science.271.5253.1247
Roderick, S. L. (2005). The lac operon galactoside acetyltransferase. Comptes Rendus Biologies, 328(6), 568–575. https://doi.org/10.1016/j.crvi.2005.03.005
Swigon, D., Coleman, B. D., & Olson, W. K. (2006). Modeling the Lac repressor-operator assembly: The influence of DNA looping on Lac repressor conformation. Proceedings of the National Academy of Sciences of the United States of America, 103(26), 9879–9884. https://doi.org/10.1073/pnas.0603557103
Wilson, C. J., Zhan, H., Swint-Kruse, L., & Matthews, K. S. (2007). The lactose repressor system: Paradigms for regulation, allosteric behavior, and protein folding. Cellular and Molecular Life Sciences: CMLS, 64(1), 3–16. https://doi.org/10.1007/s00018-006-6296-z
3.4 Arabinose operon
Schleif, R. (2010). AraC protein, regulation of the l-arabinose operon in Escherichia coli, and the light switch mechanism of AraC action. FEMS Microbiology Reviews, 34(5), 779–796. https://doi.org/10.1111/j.1574-6976.2010.00226.x
Schleif, R. (2022). A Career’s Work, the l-Arabinose Operon: How It Functions and How We Learned It. EcoSal Plus, 10(1), eESP00122021. https://doi.org/10.1128/ecosalplus.ESP-0012-2021
3.5 Trp operon
Blaha, G. M., & Wade, J. T. (2022). Transcription-Translation Coupling in Bacteria. Annual Review of Genetics, 56, 187–205. https://doi.org/10.1146/annurev-genet-072220-033342
Evguenieva-Hackenberg, E. (2022). Riboregulation in bacteria: From general principles to novel mechanisms of the trp attenuator and its sRNA and peptide products. Wiley Interdisciplinary Reviews. RNA, 13(3), e1696. https://doi.org/10.1002/wrna.1696
Merino, E., Jensen, R. A., & Yanofsky, C. (2008). Evolution of bacterial trp operons and their regulation. Current Opinion in Microbiology, 11(2), 78–86. https://doi.org/10.1016/j.mib.2008.02.005
Yanofsky, C. (1981). Attenuation in the control of expression of bacterial operons. Nature 289, 751-758.
3.6 Antisense RNA and Riboswitches
Pratt, L. A., Hsing, W., Gibson, K. E., & Silhavy, T. J. (1996). From acids to osmZ: Multiple factors influence synthesis of the OmpF and OmpC porins in Escherichia coli. Molecular Microbiology, 20(5), 911–917. https://doi.org/10.1111/j.1365-2958.1996.tb02532.x
Richards, J., & Belasco, J. G. (2021). Riboswitch control of bacterial RNA stability. Molecular Microbiology, 116(2), 361–365. https://doi.org/10.1111/mmi.14723
Scull, C. E., Dandpat, S. S., Romero, R. A., & Walter, N. G. (2020). Transcriptional Riboswitches Integrate Timescales for Bacterial Gene Expression Control. Frontiers in Molecular Biosciences, 7, 607158. https://doi.org/10.3389/fmolb.2020.607158 Sherlock, M. E., & Breaker, R. R. (2020). Former orphan riboswitches reveal unexplored areas of bacterial metabolism, signaling, and gene control processes. RNA (New York, N.Y.), 26(6), 675–693. https://doi.org/10.1261/rna.074997.120