Chapter 11 How Genes Are Controlled

 

I.                 Control of Gene Expression

1.     Every somatic (except the gametes) cell is produced by mitosis. Each somatic cell has the same DNA contents.

2.     Cellular differentiation is a specialization in the structure and function of cells that occurs during the development of an organism.

3.     Patterns of gene expression in differentiated cells:

                      1)    The turning on (activation) and off (inactivation) of specific genes within an organism is called gene regulation.

                      2)    Gene expression: A gene that is turned on is being transcribed into mRNA, and that message is being translated into specific proteins.

                      3)    Patterns of gene expression represent the selective patterns of gene expression in a given cell at a given time.

                      4)    Regulation of gene expression plays a central role in the development of a unicellular zygote into a multicellular organism.

4.     Gene regulation in bacteria:

                      1)    Bacteria express only the genes whose products are needed by bacteria.

                      2)    Operon represents a cluster of genes with related functions along with the promoter and operator to control their transcription in prokaryotes.

                      3)    The lac (lactose) operon was first described in the 1960s by Francois Jacob and Jacques Monod (The Nobel Prize in Physiology or Medicine 1965).

                      4)    A promoter is a DNA sequence where RNA polymerase binds to and transcription begins.

                      5)    An operator is a DNA sequence near promoter where a repressor binds to. The binding of repressor prevents RNA polymerase binding to the promoter.

                      6)    A repressor is a specific protein that blocks the transcription of operon or a gene by binding to an operator (by binding to a silencer DNA sequence in eukaryotes), while an activator is a specific protein that switches on a gene by binding to an activator binding site (by binding to an enhancer DNA sequence in eukaryotes).

                      7)    The promoter and operator together determine whether RNA polymerase can attach to the promoter and start transcribing the genes.

                      8)    The lac operon is in off mode, when there is no lactose around (and in the presence of glucose).

                      9)    The lac operon is in on status, when lactose is present (and in the absence of glucose). Lactose binds to the repressor and change the conformational shape of the repressor. The lactose-bound repressor is inactive and fails to bind to the operator.

5.     Gene regulation in eukaryotes:

                  1)        Eukaryotes have more complicate mechanisms than bacteria for regulating the expression of their genes.

                  2)        The initiation of transcription is the most important stage for regulating gene expression in eukaryotes.

                  3)        Most eukaryotic genes have individual promoters and other control sequences. Eukaryotic genes are generally not organized into groups as operons.

                  4)        Specific transcription factors, such as activators and repressors, bind to enhancer and silencer DNA sequences to increase and decrease gene expression, respectively.

6.     Different mRNA molecules producing from the same one primary transcript is called alternative RNA splicing.
 7.     RNA interference (RNAi), also called post transcriptional gene silencing (PTGS), is a process used to silence the expression of specific genes.  Andrew Fire and Craig Mello were awarded a Nobel Prize in 2006.
8.     Post-translational control mechanisms often involve cutting polypeptides into smaller, active final products, in eukaryotes. For example, the insulin is synthesized as one long, inactive preproinsulin (preproinsulinà proinsulinà insulin).
 9.     A signal molecule (for instance, a water-soluble hormone) can act by binding to a receptor protein and initiating a signal transduction pathway, a series of molecular changes that convert a signal to a specific response inside the target cell.
10.  Homeotic genes (Homeogenes) are master control genes that determine what body parts will develop in which locations.
11.  DNA microarray is a glass slide containing thousands of single-strain DNA fragments arranged in an array. Complementary DNA (cDNA) is reverse-transcribed in vitro using mRNA as a template and reverse transcriptase, corresponding to a eukaryotic gene but lacks the introns.  Reverse-transcription is a process that generates cDNA from an RNA template by a reverse transcriptase (RT, RNA-dependent DNA polymerization).

II.               Cloning of Plants and Animals

1.     Reproductive cloning: nuclear transplantation is a technique in which the nucleus of one cell is placed into another cell whose nucleus has been removed. The cell is then stimulated to grow, producing an embryo.

2.     Therapeutic cloning is not to produce an organism, but to produce embryonic stem (ES) cells. Stem cells are unspecialized cells with totipotency that can generate one or more types of specific cells. Totipotency is the ability of a single cell to divide and produce all the differentiated cells in an organism.

III.             The Genetic Basis of Cancer

1.     Oncogene is a cancer-causing gene, contributing to malignancy by abnormally enhancing the amount or activity of a growth factor made by the cell.

2.     Proto-oncogene is a normal gene with the potential to become an oncogene.

3.     In 1976, J. Michael Bishop and Harold Varmus (The Nobel Prize in Physiology or Medicine 1989) found that Rous sarcoma virus causing sarcoma cancer in chickens contains a src oncogene (v-src; for viral sarcoma) that is an altered version of a normal chicken gene (protein tyrosine kinase gene; c-src; for cellular sarcoma, a proto-oncogene).

4.     Tumor-suppressor gene: its gene product inhibits cell division, preventing uncontrolled cell growth, e.g., p53 and Rb (retinoblastoma gene).

5.     The development of a cancer is a gradual process.

1)     Multiple genetic changes are needed to develop a cancer cell.

2)     Colon cancer begins when an oncogene is activated through mutation.

3)     Additional DNA mutations cause the growth of a small benign tumor in the colon wall.

4)     Further mutations eventually lead to formation of a malignant tumor that has the potential to metastasize. Metastasis is the spread of cancer cells beyond their original site.

6.  Faulty proteins can interfere with normal signal transduction pathways.

7.  Cancer is the second-leading cause of death (after heart disease) in most industrialized nations. Carcinogens are agents that alter DNA and make cells cancerous. For instance, exposure to mutation-causing UV radiation from the sun is known to cause skin cancer, including a deadly type called melanoma.