3C1

1. 3C1 CHANGES IN GENOTYPE CAN RESULT IN CHANGES IN PHENOTYPE

2. DNA REPAIR • Cells are constantly exposed to DNA-damaging agents • Errors from replication and damage induced by agents such as UV light and chemical mutagens can lead to mutations

3. DNA repair restores damaged DNA • Without repair mechanisms, cells would accumulate mutations until inviability (inability to live and reproduce) occurred

4. Repair can be either specific or nonspecific. • Photorepair (specific)The enzyme photolyase uses energy from visible light to cleave thymine dimers (one particular type of damage by UV light – thymine dimers cause thymine molecules to covalently link together). Excision repair is nonspecific. In prokaryotes, the uvr (type of protein)system can remove a damaged region of DNA.

5. Repair of thymine dimer by photorepair

6. Repair of damaged DNA by excision

7. DNA Repair • Errors due to replication • DNA polymerases have proofreading ability • Mutagens – any agent that increases the number of mutations above background level • Radiation and chemicals • Importance of DNA repair is indicated by the multiplicity of repair systems that have been discovered

8. DNA Repair • Falls into 2 general categories • Specific repair • Targets a single kind of lesion in DNA and repairs only that damage • Nonspecific • Use a single mechanism to repair multiple kinds of lesions in DNA

9. Photorepair • Specific repair mechanism • For one particular form of damage caused by UV light • Thymine dimers • Covalent link of adjacent thymine bases in DNA • Photolyase • Absorbs light in visible range • Uses this energy to cleave thymine dimer

10. Excision repair • Nonspecific repair • Damaged region is removed and replaced by DNA synthesis • 3 steps • Recognition of damage • Removal of the damaged region • Resynthesis using the information on the undamaged strand as a template

11. The Process of Development • Development is the sequence of systemic, gene-directed changes throughout a life cycle. The four subprocesses of development are: • Growth • Cell differentiation • Pattern formation • Morphogenesis

12. Mutations: Altered Genes • Point mutations affect a single site in the DNA • Base substitutions exchange one base for another, and frameshift mutations involve the addition of deletion of a base. Triplet repeat expansion mutations can cause genetic diseases. • Chromosomal mutations change the structure of chromosomes • Chromosomal mutations include additions, deletions, inversions, and translocations. • Mutations are the starting point of evolution. • Our view of the nature of genes has changed with new information.

15. Frameshift mutations • Addition or deletion of a single base • Much more profound consequences • Alter reading frame downstream • Triplet repeat expansion mutation • Huntington disease • Repeat unit is expanded in the disease allele relative to the normal

16. Chromosomal mutations • Change the structure of a chromosome • Deletions – part of chromosome is lost • Duplication – part of chromosome is copied • Inversion – part of chromosome in reverse order • Translocation – part of chromosome is moved to a new location

19. Mutations are the starting point for evolution • Too much change, however, is harmful to the individual with a greatly altered genome • Balance must exist between amount of new variation and health of species

20. Sickle cell anemia is caused by an altered protein

21. Malaria resistance by the sickle cell trait (genotype HbAS) has served as the prime example of genetic selection for over half a century. Nevertheless, the mechanism of this resistance remains the subject of considerable debate. While it probably involves innate factors such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity.