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Chapter 11 Gene Expression 1. Define the term gene expression. A. The genome – the complete genetic material contained within an individual B. Gene expression is the activation of a gene that results in the formation of a protein 1) A gene is said to be “expressed,” or turned “on,” when transcription occurs 2) Cells use information in genes to build hundreds of different proteins, each with a unique function, but not all proteins are required by the cell at one time By regulating gene expression, cells are able to control when each protein is made a. Some proteins play structural roles, others are enzymes, some serve only in immune responses b. We don’t want genes (proteins being made) turned on if we don‘t need them C. Gene expression occurs in two steps, transcription and translation 1) Gene expression begins when the enzyme RNA polymerase transcribes the DNA nucleotide sequence of a gene into a specific mRNA 2) During translation, this mRNA then migrates to a ribosome, where it is translated into a specific protein 2. Describe the regulation of the lac operon in prokaryotes. A. Protein synthesis in Prokaryotes is controlled by “On-Off” switches 1. When you eat or drink a dairy product, E. coli in your stomach absorbs the lactose and breaks down into it’s 2 parts, glucose and galactose. This requires 3 different enzymes, which are each coded for by 3 different genes. 2. There is an “on-off” switch that transcribes and then translates the 3 genes when lactose is present, and “turns off” the gene when lactose is not there (Operator). 3. There is a promoter, which is a DNA sequence that recognizes the enzyme RNA polymerase, and thus promotes transcription. 4. There are structural genes present that code for particular polypeptides (enzymes) to be made when lactose is present. a. A group of genes that code for enzymes involved in the same function (structural genes), their promoter site, and the operator, all make up the operon. b. The operon that controls the metabolism of lactose is called the lac operon. B. Repression 1. When there is no lactose present, a protein called a repressor turns off the operon. a. A repressor is a protein that binds to an operator and physically blocks RNA polymerase from binding to a promoter site (it inhibits the gene from being expressed). C. b. The blocking of RNA polymerase consequently stops the transcription of the genes in the operon. 1) The process by which a repressor inhibits transcription is called repression. a) Transcription of the structural genes is ultimately controlled by a regulator gene, which codes for the production of the repressor protein. Activation 1. When lactose is present, the lactose binds to the repressor and changes the shape of the repressor. The change in shape causes the repressor to fall off of the operator. Now RNA polymerase can attach to the promoter and being transcribing the genes that code for lactose-metabolizing enzymes. a. Because it activates, or induces, transcription, lactose acts as an inducer. 1) Inducer – a molecule that initiates gene expression. a) The initiation of transcription by removal of the repressor is called activation. 3. Distinguish between introns and exons. A. The Control of Protein Synthesis in Eukaryotes is Complex 1. Eukaryotes are vastly different from prokaryotes. Our genomes are much more complex than those of prokaryotes. We have DNA found in chromosomes of every cell. We also have different cells performing different functions, so we don’t need them all expressing the same genes (making the same proteins). 2. Eukaryotic cells must also turn on and off their genes. 3. Because a nuclear envelope separates transcription from translation, more opportunities exist for regulating gene expression. B. Structure of a Eukaryotic Gene 1. Much of the control of gene expression in eukaryotes occurs at the level of the individual chromosome. a. Gene expression is partly related to the coiling/uncoiling of DNA. 1) Right before cell division (mitosis or meiosis), DNA coils around histones to form chromosomes. After cell divisions, DNA uncoils. This uncoiled form of DNA is called euchromatin, and is the site of active transcription of DNA into RNA. a) So that the entire genome doesn’t get transcribed and translated, some of the DNA remains coiled. This prevents it from getting “read”, thus, it is not expressed. The amount of uncoiled DNA therefore dictates the degree of gene expression. C. Genes in Eukaryotes often have Intervening DNA 1. As in prokaryotes, the promoter is the binding site of RNA polymerase. After the promoter, eukaryotes have other kinds of genes, introns, and exons. a. In eukaryotes, many genes are interrupted by introns, which are long segments of nucleotides that have no coding information. b. Exons are portions of a gene that are translated (expressed) into proteins. D. Control after Transcription 1. After eukaryotic genes are transcribed (in the nucleus), the mRNA passes through the nuclear envelope into the cytoplasm, to be translated. a. Before the mRNA leaves the nucleus, it needs to be modified. b. The mRNA made immediately after transcription contains both introns and exons (pre-mRNA). 1) The introns in the resulting Pre-mRNA are cut out by enzymes. 2) The remaining exons are “stitched” (spliced) back together to form a smaller mRNA molecule that is then translated. 3) End result, mRNA made of only exons. This mRNA is what leaves the nucleus to be translated into proteins. 4) Remember: proteins are made on ribosomes. Notes: c. Each exon encodes for a different part of a protein. d. Cells can occasionally shuffle exons between genes and make new genes. 1) Example: your cells have 12 different hemoglobin genes, all of which arose as duplicates of one ancestral hemoglobin gene. 4. Describe the role of enhancers in the control of gene expression. A. Enhancer Control 1. Eukaryotic genes on a DNA strand also have noncoding control sequences that facilitate transcription. Such a noncoding control sequence is called an enhancer. a. An enhancer must be activated for its associated gene to be expressed. 2. Transcription factors help arrange the RNA polymerases in the correct position by the promoter, thus regulating transcription. a. A loop in the DNA brings the enhancer with its activator in contact with RNA polymerase and it’s promoter. b. Transcription factors bound to enhancers are now able to activate transcription factors bound to the promoter. 5. Recognize the relationship between gene expression and morphogenesis. A. Gene Expression and Development 1. The control of gene expressions plays an important role in the growth of eukaryotes as different cells become specialized to perform tasks. 2. Cell Differentiation a. All multicellular sexually reproducing organisms begin life as a zygote. b. Only a fraction of the genes are expressed at any given time throughout life. c. Cells become specialized throughout an organism’s life cycle. d. This specialization is called cell differentiation. 1) As an organism grows and develops, organs and tissues develop to produce a characteristic form. a) This development of form is called morphogenesis. 3. Homeotic Genes a. Are regulatory genes that determine where certain anatomical structures, such as appendages, will develop in an organism during morphogenesis. 1) The specific DNA sequence that codes for this organization/development/placement is called a homeobox. a) Mutations that occur in homeoboxs can have devastating consequences. i. Legs coming out of eye sockets, etc. 6. List the key characteristics of cancer cells. A. Cancer is the uncontrolled growth of cells, due to bypassing the checkpoints within the cell cycle 1. Cancer cells continue to divide even when they are very densely packed, seemingly ignoring the normal cellular message to stop dividing. 2. They also continue dividing after they are no longer attached to other cells, a trait that facilitates the spread of cancer cells throughout the body. B. A tumor is an abnormal proliferation of cells that results from uncontrolled, abnormal cell division. 1. A benign tumor remains within in a mass and is usually not deadly. 2. A malignant tumor is the type of tumor that grows and spreads elsewhere in the body. Malignant tumors are generally called cancer. 3. Metastasis is the spread of cancer cells beyond their original site. C. Kinds of cancer 1. Malignant tumors can be categorized according to the types of tissues they affect. a. Carcinomas – grow in the skin and the tissues that line the organs. i. Examples: lung and breast cancer. b. Sarcomas – cancer of the bones and muscles. c. Lymphomas – solid tumors that grow in the tissues of blood cells. i. Leukemia – the uncontrolled production of white blood cells. D. Causes of Cancer 1. Growth factors – regulatory proteins that ensure that the events of cell division happen in the correct sequence and at the correct rate. 2. A carcinogen is any substance that increases the risk of cancer. a. Examples: tobacco, UV radiation, ionizing radiation (X-rays), etc. 3. A mutagen is an agent that causes mutations to occur within a cell. a. Example: asbestos 4. Usually, more than 1 mutation is needed to get cancer. E. Oncogenes 1. A gene that causes cancer or other uncontrolled cell proliferations. 2. They begin as normal genes, called proto-oncogenes, which control a cell’s growth and differentiation. a. A mutation in a proto-oncogene may cause it to produce more protein or a protein that seems to be unusually active in triggering cell division. 3. Some genes suppress tumor formation. These genes are called tumor-suppressor genes. a. Sometimes there are mutations in these genes that causes the proteins they make to not work, thus, cancer forms. F. Viruses and Cancer 1. Certain viruses can cause cancer in plants and animals. Many viral genes are actually oncogenes. 2. They can also stimulate uncontrolled growth of cells in their hosts. a. In humans, some viruses cause leukemia, others cause cervical cancer. Chapter 11 Gene Expression Gene expression is the activation of a gene that results in the formation of a protein. Only a fraction of any cell’s genes are expressed at any one time. Structural genes code for a particular product. Regulatory elements (a promoter and an operator) regulate the transcription of structural genes. In prokaryotes, the structural genes, the promoter, and the operator collectively form an operon. A promoter is the segment of DNA that recognizes the enzyme RNA polymerase and thus promotes transcription. An operator is the segment of DNA that can block transcription and thus prevent protein synthesis from occurring. In the bacterium E. coli, the lac operon codes for the three enzymes required for lactose metabolism. A repressor protein can inhibit a specific gene from being expressed. The blockage of transcription by the action of a repressor protein is called repression. A regulator gene controls the expression of a particular gene by coding for a repressor protein. An inducer is a molecule that initiates gene expression. In E. coli, lactose serves as an inducer. Eukaryotes do not have operons. The genomes of eukaryotes are larger and more complex than those of prokaryotes. Eukaryotic genes are organized into noncoding sections called introns and coding sections called exons. An enhancer must be activated for a eukaryotic gene to be expressed. Transcription factors initiate transcription by binding to enhancers and RNA polymerases. The development of specialized cells is called cell differentiation. The development of form in an organism is called morphogenesis. Both cell differentiation and morphogenesis are governed by gene expression. Homeotic genes are regulatory genes that determine where anatomical structures will be placed during development. Within each homeotic gene, a specific DNA sequence known as the homeobox regulates patterns of development. The homeoboxes of many eukaryotic organisms appear to be very similar. Cancer is the uncontrolled growth of abnormal cells. Cancerous cells may form a tumor. Tumors may be benign or malignant. A carcinogen is any substance that increases the risk of cancer. Mutagens are substances that cause mutations. Mutations of proto-oncogenes or tumor suppressor genes may lead to cancer. Some viruses can cause cancer. Vocabulary List Activation Benign tumor Cancer Carcinogen Carcinoma Cell differentiation Enhancer Euchromatin Exon Gene expression Genome Growth factor Homeobox Inducer Intron lac operon Leukemia Lymphoma Malignant tumor Metastasis Morphogenesis Mutagen Oncogene Operator Operon Pre-mRNA Proto-oncogene Regulator gene Repression Sarcoma Structural gene Transcription factor Tumor Tumor-suppressor gene