Regulation Of The Lactase Gene

Key Concepts • Eukaryotic gene expression is regulated at the levels of transcription, RNA processing, translation, and post-translation. • Proteins called transcription factors bind to DNA and control transcription. Different types of transcription factors can increase or decrease transcription. • Mutations in DNA regions that control gene expression can alter the way genes are expressed. • Infants have high lactase levels so that they can digest their mothers’ milk, but lactase gene expression is turned off after weaning. • Lactase persistence is the trait that allows adults to continue to digest milk. It results from a mutation in an enhancer region of the lactase gene. Questions 1. What is the difference between lactose tolerance and lactose intolerance? Be specific. The main difference between lactose tolerance and lactose intolerance is the ability to digest lactose, a carbohydr ate commonly found on dairy products, to its simpler units – glucose and galactose through the enzyme lactase. Basically, a person is considered lactose intolerant is he/she does not have/ have reduced lactase in his/her small intestine. 2. Why is lactose tolerance also called lactase persistence? Lactase is a normal enzyme found in the human body most especially during its infant to childhood stages. As we age, the ability to produce the enzyme reduces and in some cases it completely stops. This makes a person lactose intolerant. Lactose tolerance is also called lactase persistence because these people did not stop from producing lactase even post childhood stage. They have persistently produced this enzyme which allow the person to easily digest dairy products with ease. 3. In which cells or tissues is lactase produced and what is its role? Lactase is primarily produced in the cells of the walls of the small intestine. The small intestine functions for the absorption of nutrients from digested food as well as further digestion of food. To be more specific, proteins, fats, and carbohydrates are digested here with the help of many gastric juices. Hence, lactose is one of the carbohydrates that is digested in the small intestine with the help of lactase. 4. What normally happens to the levels of lactase produced throughout a person’s lifetime? LCT gene, the gene responsible for the translation of lactase, is very active during infant to childhood stage. As a person ages, the LCT gene becomes inactive thus greatly affecting the production of lactase. In general, as a person gets older, the more the person becomes lactose intolerant. 5. In general, why is it important for a cell to regulate protein production? Generally, cells have to regulate protein production to balance out the demand and supply of the body. Higher or lower than the optimal protein concentration may lead to unwanted effects in certain situations. In some organisms, deficiency on production of protein may lead to overexpression or under expression of a certain trait – thus labelling them as “abnormal”. 6. What are the steps in gene expression that ultimately affect protein levels in a eukaryotic cell? Gene expression involves 3 main stages – replication, transcription, and translation. Protein regulation occurs in stages from the transcription of DNA to RNA until post-translational stages. During transcription, transcription factors (TF) including the presence of activators and repressors can affect the conversion of LCT gene into mRNA protein. Alternate splicing may also interfere as splicing of alien or different exons may occur. During translation, RNA interference may bind to the mRNA molecule which may trigger the degradation of the usable mRNA molecule or may also play to block the translation process. Post-translational protein regulation may also be key factors to reduce protein levels with the presence of proteasomes. 7. What is the role of general transcription factors and where do they bind? The general transcription factor allows the start of the transcription process. It binds to the at the promoter region of the DNA to enhance the assembly of RNA polymerase and the DNA thus subsequently start the transcription process. Hence, without the general transcription factors, no RNA transcription will occur. 8. How do activators and repressors affect transcription? Activators and repressors do affect the rate of transcription in different ways. Activators can increase the rate of translation by helping the general transcription factors to bind easily with RNA polymerase. On the other hand, repressors inhibit transcription by mediating between the general transcription factor-RNA polymerase interaction thus preventing transcription to occur. 9. Where do activators bind? Activators bind at the enhancer region which is few blocks before the promoter region. The presence of activators may also help in uncoiling the DNA strand, promoting transcription to occur. 10. What are two ways in which repressors can interfere with transcription? Repressors may interfere in two ways. (1) Repressors may inhibit the binding of the general transcription factor and RNA polymerase. This complex is important in the initiation stage of RNA transcription, without this complex, no transcription will occur. (2) Repressors may promote coiling of the DNA strand. A coiled DNA strand is an indication that it cannot be proceed transcription. 11. Multicellular organisms are made up of different types of differentiated cells. Given that all cells in an organism have the same DNA—and thus the same genes—explain how it is that different genes can be expressed only in certain types of cells. Multicellular organisms may have differentiated cells they do all contain the same exact copy of DNA yet, they do not express all genes present in the genome. Gene regulation occurs in the proper assignment of gene expression in every cell. Some genes are “turned on” and “turn off” in each type of cell. 12. Is RNA processing a common way for regulating gene expression? Yes. Post-transcriptional processing involves the splicing of the premature mRNA molecule in preparation for translation. 13. What is alternative splicing and why is it important? Alternate splicing involves the splicing of different exons together. To be specific, this involves the rearrangement of different exons thus producing different combinations. This is important in enriching/diversifying the pattern of gene expression in eukaryotes. 14. What is translation? Translation is the process by which sequences from mature mRNA molecules are read and translated into amino acids which is a building block of protein. 15. RNA interference is a major mechanism of gene regulation in eukaryotes. Explain how RNA interference works. Small pieces of RNA bind to mRNA to trigger degradation or block translation. This maneuver cancels out the further gene expression. 16. Which proteins are marked for destruction? Cells that are no longer important in the physiology of the body and are damaged are marked for destruction. 17. How does a cell know which proteins should be destroyed? Proteins tagged with ubiquitin, a regulatory protein which is also involved in the synthesis of new proteins, are markers for destruction. 18. How are these proteins destroyed? Proteins are marked with ubiquitin for degradation. In some cases, additional ubiquitins are added to the protein to easily recognize the protein which will be degraded. Proteasomes are large, multisubunit protease complex tasked to destroy the proteins marked with ubiquitin. 19. At what level (i.e., transcription, translation, or protein processing) is the lactase gene (LCT) regulated? Lactase gene (LCT) is regulated mostly at the transcription level. Yet, according to the source, the study of regulation of LCT gene has not yet fully known. 20. Using your knowledge of activators and repressors, hypothesize two ways in which transcription of the LCT gene could be turned off. (1) Transcription may be turned off by the presence of more repressors. The higher the number of repressors, the more it will over power the concentration of activators thus inhibiting transcription of LCT gene. (2) The decrease in the concentration of activators may also be a factor to empower the repressors instead. The lesser the activator, the slower the rate of gene expression will be. 21. In what regions of the world is lactase persistence most prevalent? Northern Europe and nearby regions of Africa. 22. How is lactase persistence an example of human evolution? It has been found out that our ancestors do not have this mutation in the LCT gene before. It has been a result of human’s adaptation with new food source from domesticated animals – specifically milk. If human did not have this kind of evolution, we are not able to consider animal milk as another source of food since it can bring indigestion and discomfort brought by lactose intolerance. Subsequently, geneticists had related that the mutation of the LCT gene progressed to the progress in cattle domestication. 23. Explain the effect of the mutation that occurs among northern European people on LCT gene expression. Population with LCT gene expression in Northern Europe tend to tolerate milk drinking even at an older age. With this adaptation, people had become more creative in making new food advancement involving milk as well as agriculture on animals producing this product. I do believe that with the adaptation, food security has expanded in these areas as they find refuge on new food sources. 24. What are the similarities and differences between the lactase persistence mutations found in African populations and the one found in European populations? (Consider, for example, type of mutation, location, function.) Both the European and African version of mutation had it at the enhancer region of the LCT gene. Meaning, both variants mutated at the enhancer region which is blocks away from the promoter region of the said gene. Both mutations are also examples of substitution. In the European variant, C is changed to T which led to lactase persistence while G is changed to C in the African variant. Despite their differences, both mutations expressed the same adaptation – the continuous expression of LCT gene leading to production of lactase and tolerance of lactose when digesting lactose-rich food.