Mutations

1. Mutations

2. Categories of Mutations by Type • Deletions • Inversions • Insertions • Duplications • Point mutations • Change of a single nucleotide in the DNA • Nucleotide change – transition or transversion • Single nucleotide insertion • Single nucleotide deletion

3. Categories of Mutations by Affect • Regulatory • Affect production or steady state levels of gene product • promoters, splicing sequences, ribosome binding sites • Structural (Coding) • Affect actual sequence of gene product • point mutations within coding sequence • Silent • a change in DNA sequence that has no detectable affect on gene expression or gene product function • SNP – single nucleotide polymorphisms

4. Point Mutations in Coding Sequences Missense – changes amino acid Nonsense – creates stop codon Frameshift – alters remainder of reading frame results in completely different amino acid sequence.

5. Base Changes • Transitions • pyrimidine replaces pyrimidine - C to T or T to C • purine replaces purine – G to A or A to G • GC changed to A=T or vice versa • Most common base change • Transversion • purine replaces pyrimidine or vice versa • G to C or T • A to C or T • C to G or A • T to G or A • GC changed to CG or T=A • Rare

6. Tautomeric Shifts Lead to Transitions Figure 16.10

7. Normal amino-A = keto-T amino-C  keto-G Tautomeric imino-A = amino-C amino-A = imino-C enol-T  keto-G keto-T  enol-G Tautomeric Base-Pairing

8. Tautomeric Shifts Alter Base-Pairing Specificity

9. Tautomer Figure 16.10

10. Modification of Bases by Alkylating Agents EMS – ethylmethane sulfonate DMS – Dimethyl sulfonate ENU - Ethylnitrosourea

11. Alkylation Leads to Transitions

12. Deamination leads to Transitions

13. Oxidative DNA Damage Leads to Transversion Mutations free radicals

14. Intercalation Leads to Insertions/Deletions

15. Ionizing Radiation DNA Damage VIS

16. Shortwave UV (UVA) Causes Thymidine Dimers

17. X-rays & γ-rays Cause DNA Strand Breaks