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Chapter 7. Gene Expression and Control Part 4. Eukaryotic Gene Controls. All of the cells in your body are descended from the same fertilized egg and, therefore, have the same DNA and genes.
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Chapter 7 Gene Expression and Control Part 4
Eukaryotic Gene Controls All of the cells in your body are descended from the same fertilized egg and, therefore, have the same DNA and genes. Some of these genes are transcribed by all cells in your body-genes such as those that control structures and chemical pathways that are common to all cells. However, all cells in your body have specialized in some ways to perform specific tasks. They have differentiated.
Eukaryotic Gene Controls Differentiation is a process by which cells become specialized. It occurs when some cells begin to express different subsets of their genes, while turning other subsets “off”. The genes that a cell expresses determines which molecules it will produce and, therefore, what kind of cell it will become. For example, while most cells, no matter what kind, express genes that code for the production of enzymes that will perform the energy producing reactions of cell respiration, only red blood cells express the genes that code for the production of the globin chains found in hemoglobin.
Eukaryotic Gene Controls A cell usually uses no more than 10% of its genes at any one time. Which genes are being expressed at any given time are determined by many factors, including the type of cell it is, as well as conditions both inside and outside of the cell. These factors affect the control of gene expression from transcription to translation and even to the delivery of the mRNA or protein to its final destination.
Eukaryotic Gene Controls Such control includes processes that start, enhance, slow, or stop gene expression. Proteins called transcription factors determine whether and how fast genes will be transcribed when they bind directly to DNA. Some transcription factors inhibit the binding of RNA polymerase to a promoter in front of a gene. This inhibits the transcription of the gene. Other transcription factors help RNA polymerase to bind to the promoter, thus increasing the rate of transcription of the nearby gene.
Homeotic Genes Homeotic genes control the formation of specific body parts. All homeotic encode the production of transcription factors containing a homeodomain. A homeodomain is a region of about 60 proteins that contains about 60 amino acids and allows the protein to bind to a promoter or some other DNA sequence. Homeotic genes are a kind of master gene because their products affect the expression of other genes.
Homeotic Genes The expression of a master gene allows for the expression of other genes, resulting in the production of an intricate body part such as an eye. • Homeotic genes- “…a group of genes act synergistically to coordinate the process of segmentation and subsequent specialization in the developing embryo.” • http://eweb.furman.edu/~wworthen/bio111/evodevo.htm
Homeotic Genes “Changes in these genes (ie. homeotic genes) can have profound effects on the final morphology of a segment. And because these genes encode transcription factors that are binding to MANY genes in the same cell, there are correlated and co-ordinated responses among the genes in a cell and the cells in that segment. Consider the "antennapedia" gene in Drosophila. It is "on" in the thoracic segments of a developing fly pupa during metamorphosis. The gene product - a transcription factor - stimulates the production (expression) of a myriad of genes that leads to the development of muscle, nerve, and exoskeleton tissue in the shape of a leg. This gene is normally off in the head and abdominal segments, so legs don't develop there. However, mutants occur that express this gene in the head segment that usually gives rise to the antennae. In these individuals, the activation of the gene causes the development of legs on the head - where antennae should be.” http://eweb.furman.edu/~wworthen/bio111/evodevo.htm
Homeotic Genes The function of many homeotic genes was discovered by manipulating their expression, using gene knockout, one at a time. Gene knockout involves researchers inactivating a certain by either deleting it or introducing a mutation into it. They then observe how the organism in which this gene knockout has been performed is different from a “normal” individual. Any differences observed give the scientists clues as to the function of the missing gene product.
Homeotic Genes Homeotic gene are expressed in animals during embryonic development. The process begins long before body parts develop, as these master genes are expressed in local areas of the embryo. The result is a concentration gradient of master gene products that span the entire embryo. The location of embryonic cells in this gradient determine which homeotic genes will be transcribed in each cell. Product from the homeotic genes cause each cell to differentiate into tissues that will form a head, a wing, an eye, or a leg.
Homeotic Genes • Researchers often name homeotic genes based upon what happens in their absence (ie. when they have been “knocked out”). • Examples: In frutiflies, • Eyeless gene: controls development of eyes • Dunce gene: required for learning and memory • Wingless gene • Wrinkled gene • Minibrain gene • Groucho gene • Toll gene: “toll” in German means “cool”, which is what one German researcher meant when he saw the disastrous effects of the mutation of this homeotic gene; affects immune system, resulting in death of fly by fungal infection
Homeotic Genes Wild type Wild type minibrain Eyeless toll groucho Wild type
Homeotic Genes Homeotic genes control development by the same molecular mechanisms in all eukaryotes. Many are interchangeable among different species. Homeodomains differ among species by only a single amino acid substitution. These facts lead scientists to infer that they evolved in ancient eukaryotic cells.
Homeotic Genes For example, humans, squid, mice, fish, and many other animals have a homeotic gene called PAX6, which is similar to the eyeless gene in fruit flies. Mutations in this gene in humans result in eye disorders such as aniridia, a condition in which a person’s irises are underdeveloped or missing. PAX6 also works across different species. If a PAX6 gene from a human is inserted into an eyeless mutant fly, it will cause an eye to form wherever it is expressed. This provides evidence that there may be a shared ancestor among distantly related animals such as fruit flies and humans.
Sex Chromosome Genes As we have discussed previously, in humans and other mammals, females contain XX sex chromosomes, while males contain XY sex chromosomes. In females, one X chromosome is always tightly condensed so that RNA polymerase cannot access its genes to transcribe them. This tightly condensed unexpressed X chromosome is referred to as a Barr body. Barr bodies are what cause many female cats to be multicolored (or calico). Since males have only one X chromosome to express, this inactivation of one X chromosome in females ensures that females express only one of their X chromosomes, thus equalizing the expression of X chromosome gene between the sexes. This is called the dosage compensation theory.
Sex Chromosome Genes The human X chromosome contains 1,336 genes. Some of these genes are associated with sexual traits such as the distribution of body fat and hair. However, most genes on the X chromosome control nonsexual traits such as blood clotting and color perception. Such genes are expressed in both males and females.
Sex Chromosome Genes The human Y chromosome contains only 307 genes, but one of them is the SRY gene. This gene is the master gene for male sex determination. The expression of the SRY gene in an embryo results n the formation of testes (male gonads). Cells of the testes then make testosterone, hormone which then controls male secondary sexual characteristics such as facial hair, increased muscle mass, and a deep voice. It was determined the function of the SRY gene by gene knockout. Mutations in this gene result in development of external genitalia that appear female.
Sex Chromosome Genes A female (XX) embryo has no Y chromosome, thus no SRY gene is expressed. Therefore, less testosterone is produced and so ovaries form. Ovaries, in turn, make estrogen which results in the development of female secondary sexual characteristics such as enlarged, functional breasts.
Cancer: Gene Expression Out of Control Cells all over your body are constantly dividing to replace worn out, dead, and/or dying cells. This division does not take place a t random but is tightly regulated and controlled by gene expression controls. If gene expression controls fail during the regulation of cell division, cancer (uncontrolled cell growth) is the outcome.
Cancer: Gene Expression Out of Control Cancer is the abnormal growth and division of cells that disrupts body tissues. Gene expression controls that normally keep cells from dividing to the point of overcrowding are lost, resulting in cancer cell populations of very high density such as tumors. Even though research for therapies for cancer (such as chemotherapy, radiation, surgery, etc.) abounds, cancer still causes 15%-20% of all human deaths in developed countries each year.
Cancer: Gene Expression Out of Control Cancer usually begins with a mutation in a gene whose product is part of the controls over cell growth and division. This mutation may be a new development (such as that caused by environmental agents) or it might have been inherited. If the mutation alters the gene’s protein product so that it no longer works correctly to control cell growth and division, one level of control over these processes has been lost. Even though genes that control cell growth and division normally have at least two backups (other genes whose products do the same thing), if these genes also become mutated, the cell begins to divide over and over, forming an abnormal mass called a tumor.
Cancer: Gene Expression Out of Control If tumor cells lose their membrane marker proteins that identify them as part of a certain tissue, they can actually break free from their home tissue and travel and establish themselves in other tissues in the body. This process of cancer spreading from one body tissue to another is called metastasis.
Cancer: Gene Expression Out of Control Mutations in some genes actually predispose an individual to develop certain kinds of cancer. Among these are tumor suppressor genes. Tumor suppressor genes are so named because tumors are more likely to occur in individuals who have mutations in these genes. Two examples of tumor suppressor genes are BRCA1 and BRCA2.
Cancer: Gene Expression Out of Control Mutations in one or both of these genes is associated with breast and ovarian cancer cells. If a BRCA gene mutates in one of three especially dangerous ways, a woman has an 80% chance of developing breast cancer before the age of 70.
Cancer: Gene Expression Out of Control Specifically, BRCA gene products promote transcription of genes that code for DNA repair enzymes. Any mutation that alter the function of the proteins produced from the BRCA genes alters a cell’s ability to repair damaged DNA. This means that other mutations are more likely to accumulate, eventually leading to cancer.
Cancer: Gene Expression Out of Control BRCA proteins also bind to receptors for estrogen and progesterone, which are hormones that are abundant in breast and ovarian tissues. The binding of these BRCA proteins to hormone receptors regulates the transcription of growth factor genes, which would stimulate the cells in these tissues to divide to renew breast and ovarian tissues when necessary. Mutations that result in BRCA proteins that cannot bind to hormone receptors result in growth factors being overproduced, cell division goes out of control, tissue growth becomes disorganized: cancer has developed.
Cancer: Gene Expression Out of Control Because mutations such as those in BRCA genes can be inherited, cancer is not just a disease of the elderly. There are more than 200,000 new cases of breast cancer in the U.S. each year, with about 5,700 of those occurring in women and men under 34 years of age.
Ricin and Your Ribosomes One of the toxin, ricin’s two polypeptide chains is an enzyme that removes a specific adenine nitrogen base from one of the rRNA chains of the large ribosomal subunit. When this happens, it causes the ribosome to stop working. Protein synthesis comes to a stop as ricin deactivates the ribosomes in cells and the cells begin to die. A modified form of ricin is currently being tested as a treatment for some kinds of cancer. The ricin is attached to an antibody that can locate and bind to cancer cells in the hopes that the ricin attached to this antibody would hone in and kill cancer cells without harming healthy cells.
