1. Gene Regulation and Mutation Notes and Questions How do mutations affect a cell?

2. Main Idea Gene expression is regulated by the cell, and mutations can affect this expression. Gene regulation is the ability of an organism to control which genes are transcribed in response to the environment.

3. Prokaryote Gene Regulation Prokaryotes are simple. In prokaryotes, an operon often controls the transcription of genes in response to changes in the environment. An operon is a section of DNA that contains the genes for the proteins needed for a specific metabolic pathway. A regulatory gene “turns on and off” transcription.

4. Eukaryotic Gene Regulation Eukaryotes have many more genes than prokaryotes. How is transcription controlled? Transcription factors (type of protein) ensure that a gene is used at the right time and that proteins are made in the right amount. The complex structure of eukaryotic DNA also regulates transcription.

5. Some transcription factors guide the binding of RNA polymerase to a promoter. This determines which protein will be made.

6. Hox Genes (Homeobox genes) Hox genes code for transcription factors and control differentiation – (process through which all cells become specialized in shape and function) Hox genes are used in embryo development and are active in different zones of the embryo and control what body part will develop in different parts of the embryo. Hox genes are responsible for the general body pattern of most animals.

7. RNA Interference Another way eukaryotic genes are regulated is RNA interference (RNAi). Small segments of RNA bind to mRNA and prevent parts of mRNA from being translated. (Protein Synthesis) RNA interference can stop the mRNA from translating its message. Recall that every cell contains an entire set of the organism’s DNA. Only a small segment of the DNA is used for each specialized cell to do its job. Only the part of the DNA that is needed will be used in protein synthesis.

8. Mutations A mutation is a permanent change that occurs in a cell’s DNA. A mutation in a gene sequence (protein synthesis) can change the protein that is made. Types of Mutations: ▫Point mutations, insertion, deletion

9. A mutation in DNA changes the amino acid base sequence. A different amino acid or series of amino acids are incorporated into the protein that is made on the ribosome. The result can be a malfunction of the protein. Mutated proteins often do not work. Remember the shape is very important to its function (or ability to do its “job) A mutation can affect a single nucleotide or a large segment of DNA.

10. Types of Mutations – Point Mutations Point mutations (Base-pair substitutions) - a mutation in which one nucleotide base replaces another Point mutations affect only one codon, so they affect only one amino acid in a peptide chain It may or may not have serious effects on an organism. It depends on where the mutation occurs and how it affects the protein for which it codes It can be harmless Muscular dystrophy is an example of a disease caused by a point mutation. (nonsense – early STOP codon due to the wrong amino acid) Muscular dystrophy is progressive muscle disorder characterized by the weakening of many muscles in the body.

11. Types of Mutations - Insertion Insertion is the addition of one or more bases into a nucleotide sequence This can change many amino acids in the polypeptide chain, thus changing the protein It causes a “frameshift” in the mRNA bases, thus causing the wrong amino acid to be added to the polypeptide chain. Crohn’s disease is caused by an insertion. Crohn’s is a chronic inflammation of the intestinal tract, producing diarrhea, abdominal pain, nausea, fever and weight loss.

12. Types of Mutations - Deletion Deletion – one or more bases is removed from a nucleotide sequence A different amino acid is put into the peptide chain, thus changing the protein Cystic fibrosis, a disease characterized by abnormally thick mucus in the lungs, intestines, and pancreas, is an example of a mutation caused by a deletion.

13. Frameshift Both insertion and deletion result in a frameshift. A frameshift is simply a shift (to the left or right) in the nitrogen bases, resulting in new codons. A frameshift changes the number of bases in a sequence.

14. Types of Mutations - Chromosomal Point mutations, insertions, and base deletions affect only a single gene or segment of DNA. A chromosomal mutation affects the entire chromosome. Chromosomal mutations change the number of genes in a chromosome or the organization of the chromosome. We will cover more of this with genetics.

16. The order of amino acids is similar to the order of letters and words in a sentence. If a slight change happens, the meaning can change.

17. Fragile X An example of a mutation is Fragile X. Fragile X syndrome is due to many extra repeated CGG units near the end of the X chromosome, making the lower tip of the X chromosome appear fragile.

18. Protein Folding and Stability Substitutions can lead to genetic disorders Substitutions can change both the folding and stability of the protein An example is sickle-cell disease Compare the order of the amino acids in the normal chain vs the mutated chain. What is the difference?

19. Causes of Mutation Mutations can occur spontaneously. DNA polymerase can make a mistake. Chemicals and radiation also can damage DNA. High-energy forms of radiation, such as X rays and gamma rays, are highly mutagenic. A mutagen is any agent that changes the DNA of an organism. Thymines can stick together causing a kink in the DNA. The bases will not bond correctly.

20. Body-cell v. Sex-cell Mutation Somatic cell mutations are not passed on to the next generation. Somatic cells are cells in the body that are not sex cells. Mutations that occur in sex cells are passed on to the organism’s offspring and will be present in every cell of the offspring. The mutations may not change how the cells function or may have serious effects on the organism.