Biology 205 Genetics Mutations Revisited Chapter 11

I. Definition and Importance of Mutations

A. Any heritable change in genetic material.

B. Role in evolution

C. Medical importance

II. Mutation rates.

A. Mutated alleles per locus per generation

B. Mutation rates for most human loci 1 x 10^-5 - 1X10^-6

C. Factors influencing mutation rate

1. Size of gene

2. Nucleotide sequence

3. Environmental factors

a. mutagens

b. ionizing radiation: note sources of exposure figure 11.3

III. How chemical mutatgens work

A. Base analogs

B. Chemical modification of bases(Example Nitrous acid modifies cytosine converting it to uracil pairs with adenine)

C. Chemicals that bind to DNA cause frame shift mutations. Acridine orange p 276 Intercalating agents.

IV. Detecting mutations

A. Ames test- screens for mutagens using Salmonella typhimurim mutants auxotrophic for histidine

1. Look at rate of reversion back to wild type salmonella his- -----> his+

2. Test chemicals along with liver enzymes (test for conversion of non mutagens to mutagens by liver)

3.. Mutagens are generally carcinogens but Ames tests misses some carcinogens; example styrene is a known carcinogen not picked up by the Ames test.

B. Other strategies for detecting mutations.

1. Conditional mutations: Heat sensitive mutants often due to frame shift mutations in enzymes. Yeast often used for this.

2. Resistance mutations.

3. Use haploid organisms. Yeast and other fungi useful for this.

V. General types of mutations at the molecular level.

A. Point mutations (substitutions, frameshift p 272-278)

B. Trinucleotide repeats, Gene expansion

1. Fragile x syndrome page 279 FMR-1 allele

2. Note sex related differences in transmission. Expansion of repeats in female x chromosomes not in males.

3. Progressive change in severity of symptoms from one generation to the next

4. Anticipation: expression of genetic disorder at earlier ages in succeeding generations.

C. Chromosomal mutations