Lecture 10 – DNA MutationBased on Chapter 07

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1. Introduction to DNA Mutation

2a. Adaptation versus Mutation

2b. Adaptation versus Mutation

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).

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):

• 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

• 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.

5. Reverse Mutations and Suppressor

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, G1, and G2 phases of the cell cycle

• The spontaneous mutation rate in eukaryotes is between 1024 and 1026 per gene per generation

• In bacteria and phages it is between 1025 and 1027 per gene per generation.

• Many spontaneous errors are corrected by the cellular repair systems and so do not become fixed in DNA.

7. DNA Replication Errors

8. Spontaneous Chemical Changes

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.

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

10b. Chemical Mutagens

10c. Chemical Mutagens

10d. Chemical Mutagens

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.

12. The Ames Test: A screen for Potential Carcinogens