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Genetics 5: DNA Mutations Regulation of Gene Expression Single Gene Mutations Changes in the DNA sequence of only one gene Point Mutation: just one change of one base pair. If there is a deletion or insertion of a base pair, it can cause frameshift mutation. May not have a huge effect on the coding sequence. Reading frame of the entire gene can shift one base pair over. Mutations can be referred to as either silent mutations (no altered amino acid sequence) or a missense mutation (altered amino acid sequence that still makes a protein) or a nonsense mutation (mutation that shortens a protein by prematurely adding a stop codon) Chromosome Mutations When you get a change to the entire chromosome and it may involve numerous genes. Deletion Duplication Inversion Translocation Causes of Mutations Spontaneous mutations happen naturally in the cell Some segments of DNA can actually jump from area to area within the genome. They are called transposons. Mutations can also happen due to an induced factor (mutagen). Chemical mutagens: a molecule that enters the cell’s DNA and causes substitution or frameshift changes. EG. Gasoline fumes, nitrites and compounds found in cigarette smoke Physical mutagens: physically change the DNA structure. EG xrays, UV rays. Regulation of Gene Expression Some genes are always active because they are needed for the survival of the cell. These are called constitutive genes or housekeeping genes. Other genes are turned on or off at different times depending on when they are needed by the cell. Prokaryotes: lac operon The operon is a cluster of genes grouped together under the control of one promoter. The genes that help the bacterium E.coli digest lactose are found in the lac operon. It has a regulatory region that contains the promotor for transcription, regulation sites, an operator (DNA sequence where proteins can bind onto that can stop the transcription process), and a catabolic activator protein (CAP) binding site. When there is no lactose, the lac repressor protein binds onto the operator and prevents RNA polymerase from binding to the promoter In order to start the lac operon, lactose must be present. When lactose is present, it binds onto the repressor protein and changes the shape of it so it can no longer bind onto the operator. Then the CAP activator can bind on and controls how fast the transcription works. The lac operon is known as an inducible operon because transcription is induced when lactose is present. The trp operon The operon contains 5 different genes that help code for enzymes required to make the amino acid tryptophan. Regulatory region contains a promotor and an operator region Normally, we need tryptophan, so we will transcribe the gene and there is no repressor. When we have enough tryptophan, we need to stop the transcription, and the amino acid itself will bind onto the repressor protein. This time the repressor protein will change shape so that it does fit into the operator and stop the transcription. lac vs trp Operons Regulation of Gene Expression in Eukaryotes Pre-transcriptional Control: areas not needed for transcription are wound too tightly in chromatin to be copied. Transcriptional Control: each gene has its own promoter and controls transcription with the help of activator proteins, transcription factors, enhancers and RNA polymerase Post-transcriptional control: modifications can be made to the mRNA so that the 5’ cap and the 3’ poly-A tail are not added (and do not leave the nucleus) Translational control: micro RNA and small interfering RNA can associate with protein complexes and turn off gene expression. Post-translational control: many polypeptides are not active right away. Some may need a few amino acids to be cleaved off, or adding a covalent bond in places. Questions: Page 266 # 8, 10, 12, 13. Page 272 #3 - 7, 13