1. Chapter 14 Homework is due on Sunday, January 25 at 11:59 pm The Chapter 13 and 14 test is on Monday.

2. Chapter 14 Mutations

3. You Must Know How mutations can change the amino acid sequence of a protein and be able to predict how a mutation can result in changes in gene expression.

4. Mutagens

5. Concept 14.5: Mutations of one or a few nucleotides can affect protein structure and function Mutations are changes in the genetic material of a cell or virus. Point mutations are chemical changes in just one or a few nucleotide pairs of a gene. The change of a single nucleotide in a DNA template strand can lead to the production of an abnormal protein.

7. The molecular basis of sickle-cell disease A GG Wild-type hemoglobin mRNA 5 3 Wild-type hemoglobin DNA 5 35 3 T CC T GG A CC 5 3 A GG 5 5 3 U GG 3 Normal hemoglobin Sickle-cell hemoglobin Mutant hemoglobin DNA Sickle-cell hemoglobin Val Glu

8. Hemoglobin is made up of four polypeptides. Hemoglobin alleles are codominant. What would the hemoglobin of someone who was heterozygous for sickle cell anemia be like? People who are heterozygous for sickle cell anemia don’t have the disease and they are resistant to malaria! Normal hemoglobin Sickle-cell hemoglobin Val Glu Normal polypeptide Glu Normal polypeptide Glu Sickle-cell polypeptide Val Sickle-cell polypeptide Val

9. Types of Small-Scale Mutations Point mutations within a gene can be divided into two general categories. – Nucleotide-pair substitutions. – One or more nucleotide-pair insertions or deletions.

10. Substitutions A nucleotide-pair substitution replaces one nucleotide and its partner with another pair of nucleotides. Silent mutations have no effect on the amino acid produced by a codon because of redundancy in the genetic code.

11. Figure 14.26a DNA template strand mRNA Stop Carboxyl end Protein Amino end Phe Gly Met Lys 35 5 3 5 3 Wild type TATTAAAATTCCCCG TATTAAAATTGGGCG UAUUAAAAUUGGGCG What would the amino acid sequence be in a silent mutation? Phe Gly Met Lys 3 5 53 53 Stop A instead of G Nucleotide-pair substitution: silent U instead of C TATTAAAATTCCCCA TATTAAAATTGGGTG UAUUAAAAUUGGGUG

12. Missense mutations still code for an amino acid, but not the correct amino acid. – Is sickle cell anemia a missense mutation? – Yes. Substitution mutations are usually missense mutations. Nonsense mutations change an amino acid codon into a stop codon, nearly always leading to a nonfunctional protein.

13. DNA template strand mRNA Stop Carboxyl end Protein Amino end Phe Gly Met Lys 35 5 3 5 3 Wild type TATTAAAATTCCCCG TATTAAAATTGGGCG UAUUAAAAUUGGGCG What would the amino acid sequence be if there were a nonsense mutation at the arrow? Nucleotide-pair substitution: nonsense 35 5 3 53 Met Stop A instead of T U instead of A TAATAAAATTCCCCG TATTTAAATTGGGCG UAUUUAAAUUGGGCG

14. Deletion Insertions and Deletions Insertions and deletions are additions or losses of nucleotide pairs in a gene. These mutations have a disastrous effect on the resulting protein more often than substitutions do. Insertion or deletion of nucleotides may alter the reading frame of the genetic message, producing a frameshift mutation.

15. DNA template strand mRNA Stop Carboxyl end Protein Amino end Phe Gly Met Lys 35 5 3 5 3 Wild type TATTAAAATTCCCCG TATTAAAATTGGGCG UAUUAAAAUUGGGCG What do you call it when there is a frameshift mutation that results in a stop codon at the start of a protein? Nucleotide-pair insertion: frameshift causing immediate nonsense Met 3 5 5 3 5 3 Stop Extra A Extra U TATTAAAATTCCCCG TATTAAAATTGGGCG UAUUAAAAUUGGGCG A T U

16. DNA template strand mRNA Stop Carboxyl end Protein Amino end Phe Gly Met Lys 35 5 3 5 3 Wild type TATTAAAATTCCCCG TATTAAAATTGGGCG UAUUAAAAUUGGGCG What do you call it when there is a frameshift mutation that causes a long string of amino acids to change? Nucleotide-pair deletion: frameshift causing extensive missense Leu Ala Met Lys 3 5 A 5 3 5 3 U missing TATTAA G ATTCCCCG TATTAAAATGGCG UAUUAAAAGUGGCG

17. Figure 14.26f DNA template strand mRNA Stop Carboxyl end Protein Amino end Phe Gly Met Lys 35 5 3 5 3 Wild type 3 nucleotide-pair deletion: no frameshift, but one amino acid missing Gly Met Phe 3 5 TTC 5 3 53 AG A Stop missing TATTAAAATTCCCCG TATTAAAATTGGGCG UAUUAAAAUUGGGCG TAAACCGCAATT TAGGTTCTTAAG UAUUUGGGCUAA