Lecture 2: Gene Regulation (PDF)

f. Each Protein Is Encoded by a Specific Gene ▪ DNA molecules as a rule are very large, containing the specifications for thousands of proteins. Special sequences in the DNA serve as punctuation, defining where the information for each protein begins and ends. ▪Individual segments of the...

f. Each Protein Is Encoded by a Specific Gene ▪ DNA molecules as a rule are very large, containing the specifications for thousands of proteins. Special sequences in the DNA serve as punctuation, defining where the information for each protein begins and ends. ▪Individual segments of the long DNA sequence are transcribed into separate mRNA molecules, coding for different proteins. Each such DNA segment represents one gene. A complication is that RNA molecules transcribed from the same DNA segment can often be processed in more than one way, so as to give rise to a set of alternative versions of a protein, especially in more complex cells such as those of plants and animals. ▪ Some DNA segments—a smaller number—are transcribed into RNA molecules that are not translated but have catalytic, regulatory, or structural functions; such DNA segments also count as genes. Operon refers to the combined region of the operator and structural gene. - Clusters of co-regulated genes with related functions Regions of DNA that control the production of protein such as enzyme. a. Structural gene holds the codon for the amino acid sequence found in the enzyme. b. Operator region is found in front of the structural gene. c. Promoter region is where the RNA making enzyme will bind to DNA. d. Regulator gene has a role in controlling the transcription from the structural gene. Gene therefore is defined as the segment of DNA sequence corresponding to a single protein or set of alternative protein variants or to a single catalytic, regulatory, or structural RNA molecule. ▪ The expression of individual genes in all cells is regulated: instead of manufacturing its full repertoire of possible proteins at full tilt all the time, the cell adjusts the rate of transcription and translation of different genes independently, according to need. ▪ The original transcript from the DNA is called pre-mRNA. ▪ It contains transcripts of both introns and exons. ▪ The introns are removed by a process called splicing to produce messenger RNA (mRNA) Stretches of regulatory DNA are interspersed among the segments that code for protein, and these noncoding regions bind to special protein molecules that control the local rate of transcription. a. cis-acting DNA sequences are ▪ Promoter is very close to genes regulatory elements that map initiation site. near a gene. ▪ Enhancer can lie far away from gene. - Can be reversed. - Augment or repress basal levels of transcription. b. trans-acting factors are regulatory elements that act on ▪ Genes that encode proteins the promoter or enhancer that interact directly or sequences indirectly with target genes cis-acting elements. - Known genetically as transcription factors. - Identified by: Mapping Biochemical studies to identify proteins that bind in vitro to cis-acting elements. The quantity and organization of the regulatory DNA vary widely from one class of organisms to another, but the basic strategy is universal Differences in Gene Regulation Eukaryotes Prokaryotes 1. Eukaryotic organisms have 1. Simple regulatory pathways are more complex regulatory followed. pathways. 2. Life span of prokaryotes are very 2. In eukaryotes, short term less. control and long term control - Long term control of gene of gene expression is present. expression is absent. 3. Much longer set of regulatory 3. Single and short regulatory sequence are present individually sequence is present all over the for each gene. DNA molecule. ▪ In this way, the genome of the cell—which is, the totality of its genetic information as embodied in its complete DNA sequence— dictates not only the nature of the cell’s proteins, but also when and where they are to be made. g. Life Requires Free Energy ▪ A living cell is a dynamic chemical system, operating far from chemical equilibrium. - For a cell to grow or to make a new cell in its own image, it must take in free energy from the environment, as well as raw materials, to drive the necessary synthetic reactions. - This consumption of free energy is fundamental to life. ▪ All cells need energy and matter for growth and reproduction. Some organism like plants obtain energy directly from the sun. Other organisms such as animals must consume food to obtain energy. - When it stops, a cell decays toward chemical equilibrium and soon dies. ▪ Genetic information is also fundamental to life, and free energy is required for the propagation of this information. - To specify genetic information, in the form of a DNA sequence, molecules from this wild crowd must be captured, arranged in a specific order defined by some preexisting template, and linked together in a fixed relationship. - The bonds that hold the molecules in their proper places on the template and join them together must be strong enough to resist the disordering effect of thermal motion. - The process is driven forward by consumption of free energy, which is needed to ensure that the correct bonds are made, and made robustly. - In a cell, the chemical processes underlying information transfer are more complex, but the same basic principle applies: free energy has to be spent on the creation of order. - To replicate its genetic information faithfully, and indeed to make all its complex molecules according to the correct specifications, the cell therefore requires free energy, which has to be imported somehow from the surroundings. - The free energy required by animal cells is derived from chemical bonds in food molecules that the animals eat, while plants get their free energy from sunlight. ▪ The amount of disorder in a system can be quantified and expressed as the entropy of the system: the greater the disorder, the greater the entropy. - Another way to express the second law of thermodynamics is to say that systems will change spontaneously toward arrangements with greater entropy. - Living cells—by surviving, growing, and forming complex organisms— are generating order and thus might appear to defy the second law of thermodynamics. - Where does the heat that the cell releases come from? ▪ First law of thermodynamics states that energy can be converted from one form to another, but that it cannot be created or destroyed. - The amount of energy in different forms will change as a result of the chemical reactions inside the cell, but the first law tells us that the total amount of energy must always be the same. h. All Cells Function as Biochemical Factories Dealing with the Same Basic Molecular Building Blocks ▪ All cells make DNA, RNA, and protein - all cells should possess and manipulate a similar collection of small molecules, including simple sugars, nucleotides, and amino acids and other substances that are universally required. Example: All cells require the phosphorylated nucleotide ATP (adenosine triphosphate), not only as a building block for the synthesis of DNA and RNA, but also as a carrier of the free energy that is needed to drive a huge number of chemical reactions in the cell. - Although all cells function as biochemical factories of a broadly similar type, many of the details of their small-molecule transactions differ. - Some organisms, such as plants, require only the simplest of nutrients and harness the energy of sunlight to make all their own small organic molecules. - Other organisms, such as animals, feed on living things and must obtain many of their organic molecules ready-made i. All Cells are enclosed in a Plasma Membrane across which Nutrients and Waste Materials must pass ▪ A universal feature of the cell is that: ” each cell is enclosed by a membrane—the plasma membrane.” - This container acts as a selective barrier that enables the cell to concentrate nutrients gathered from its environment and retain the products it synthesizes for its own use, while excreting its waste products. - Without a plasma membrane, the cell could not maintain its integrity as a coordinated chemical system. - The molecules that form a membrane have the simple physicochemical property of being amphiphilic—that is, consisting of one part that is hydrophobic (water-insoluble) and another part that is hydrophilic (water-soluble). - Such molecules placed in water aggregate spontaneously, arranging their hydrophobic portions to be as much in contact with one another as possible to hide them from the water, while keeping their hydrophilic portions exposed. - Under appropriate conditions, small vesicles form whose aqueous contents are isolated from the external medium.  Phospholipids have a hydrophilic (water-loving, phosphate) head group and a hydrophobic (water- avoiding, hydrocarbon) tail. - At an interface between oil and water, they arrange themselves as a single sheet with their head groups facing the water and their tail groups facing the oil. - But when immersed in water, they Formation of a membrane by aggregate to form bilayers enclosing amphiphilic phospholipid molecules. aqueous compartments. - The hydrophobic tails of the predominant membrane molecules in all cells are hydrocarbon polymers (–CH2–CH2–CH2–) but the chemical details vary. - Their spontaneous assembly into a bilayered vesicle is one of many examples of an important general principle: “Cells produce molecules whose chemical properties cause them to self-assemble into the structures that a cell needs.” ▪ Plasma membrane cannot be totally impermeable. - If a cell is to grow and reproduce, it must be able to import raw materials and export waste across its cell boundary. ▪ All cells have specialized proteins embedded in their membrane that transport specific molecules from one side to the other. - The transport proteins in the membrane largely determine which molecules enter the cell, and the catalytic proteins inside the cell determine the reactions that those molecules undergo. - By specifying the proteins that the cell is to manufacture, the genetic information recorded in the DNA sequence dictates the entire chemistry of the cell; - not only its chemistry, but also its form and its behavior, for these too are chiefly constructed and controlled by the cell’s proteins. j. A Living Cell Can Exist with Fewer Than 500 Genes Mycoplasma genitalium is a species bacterium that has one of the smallest known genome. - This organism lives as a parasite in mammals, and its environment provides it with many of its small molecules ready-made. - In spite of that, it still has to make all the large molecules—DNA, RNAs, and proteins—required for the basic processes of heredity. - It has about 530 genes, wherein 400 of which are essential. - Its genome of 580,070 nucleotide pairs represents 145,018 bytes of information. - The minimum number of genes for a viable cell in today’s environments is probably not less than 300, although there are only about 60 genes in the core set that is shared by all living species.