1. Lecture 10 – DNA Mutation Based on Chapter 07 Copyright © 2010 Pearson Education Inc.

2. 1. Introduction to DNA Mutation

3. 2a. Adaptation versus Mutation

4. 2b. Adaptation versus Mutation

5. 3. Mutations Defined A mutation is a change in a DNA base pair or a chromosome. –Somatic mutations affect only the individual in which they arise. –Germ-line mutations alter gametes, affecting the next generation. Mutations are quantified in two different ways: –Mutation rate is the probability of a particular kind of mutation as a function of time (e.g., number per gene per generation). –Mutation frequency is the number of times a particular mutation occurs in proportion to the number of cells or individuals in a population (e.g., number per 100,000 organisms).

6. 4a. Types of Point Mutations There are two general categories of point mutations: base-pair substitutions and base-pair deletions or insertions. A base-pair substitution replaces one base pair with another. There are two types (Figure 7.3):

7. Base-pair substitutions in ORFs are also defined by their effect on the protein sequence. Effects vary from none to severe. 4b. Types of Point Mutations

8. Deletions and insertions can change the reading frame of the mRNA downstream of the mutation, resulting in a frameshift mutation. 4d. Types of Point Mutation.

9. 5. Reverse Mutations and Suppressor

10. 6. Spontaneous and Induced Mutations Most mutations are spontaneous, rather than being induced by a mutagen. Spontaneous Mutations All types of point mutations can occur spontaneously during S, G 1, and G 2 phases of the cell cycle The spontaneous mutation rate in eukaryotes is between 10 24 and 10 26 per gene per generation In bacteria and phages it is between 10 25 and 10 27 per gene per generation. Many spontaneous errors are corrected by the cellular repair systems and so do not become fixed in DNA.

11. 7. DNA Replication Errors

12. 8. Spontaneous Chemical Changes

13. 9. Induced Mutations Exposure to physical mutagens plays a role in genetic research, where they are used to increase mutation frequencies to provide mutant organisms for study.

14. 10a. Chemical Mutagens Chemical mutagens may be naturally occurring or synthetic. They form different groups based on their mechanism of action: –Base analogs –Base-modifying agents –Intercalating agents

15. 10b. Chemical Mutagens

16. 10c. Chemical Mutagens

17. 10d. Chemical Mutagens

18. 11. Environmental Mutagens A wide variety of chemicals exist in our environment, and many have mutagenic effects that can lead to genetic diseases and cancer. Examples include: –Drugs. –Cosmetics. –Food additives. –Pesticides. –Industrial compounds. To be mutagenic, the chemical must enter the cell’s nucleus. Metabolism sometimes converts chemicals from a nonmutagenic to a mutagenic form.

19. 12. The Ames Test: A screen for Potential Carcinogens