3.4/7.2 DNA REPLICATION Two DNA molecules are constructed from one, therefore each new molecule contains one original strand and one new strand  a semi-conservative process Two DNA molecules are constructed from one, therefore each new molecule contains one original strand and one new strand  a semi-conservative process The original strands serve as a template for the new strand. The original strands serve as a template for the new strand. The parent and the daughter molecules are identical (all made up of the same sequence of nucleotides) The parent and the daughter molecules are identical (all made up of the same sequence of nucleotides)

DNA Replication Step 1: An enzyme (helicase) breaks the hydrogen bonds between nitrogen bases and the double helix “unzips” Step 1: An enzyme (helicase) breaks the hydrogen bonds between nitrogen bases and the double helix “unzips” Step 2: Another enzyme (DNA polymerase) moves along each strand and attaches new bases. This enzyme also proofreads the DNA for errors and may be able to correct simple errors. Step 2: Another enzyme (DNA polymerase) moves along each strand and attaches new bases. This enzyme also proofreads the DNA for errors and may be able to correct simple errors. pub/flash/24/menu.s wf DNA Replication Fork How Nucleotides are Added in DNA Replication

The Meselson-Stahl Experiment Meselson and Stahl Experiment

Errors in Replication Mutations are heritable changes in DNA, which can be passed on to future generations. They can occur in any gene and randomly. Mutations are heritable changes in DNA, which can be passed on to future generations. They can occur in any gene and randomly. Nondisjunction Nondisjunction Any one gene has a one in a million chance to be mutated. We have so many genes that mutations are fairly common. Each of us carries several mutations in our bodies. Any one gene has a one in a million chance to be mutated. We have so many genes that mutations are fairly common. Each of us carries several mutations in our bodies. Causes may include radiation and exposure to chemicals, viruses… Causes may include radiation and exposure to chemicals, viruses… Mutations can be: Mutations can be: 1. Useful (positive) 2. Harmful (negative) 3. No effect (neutral)

POINT MUTATIONS Changes in one or two bases Point mutations can be divided into 2 general categories: base-pair substitutions and base-pair insertions or deletions (frameshift mutations)

Base Substitutions: Involves a change in one of the bases. These could be: Base Substitutions: Involves a change in one of the bases. These could be: a) Silent: no effect, codes for the same amino acid b) Missense: altered amino acid sequence, varying severity (sickle-cell, colourblindness, hemophilia)  translations will be terminated prematurely c) Chain Termination/ Nonsense: produces a stop codon and stops production of protein  leads to non-functioning proteins Animation Quiz 3 - Mutation by Base Substitution

Frameshift Mutation: Addition or deletion of bases; codons are shifted out of place Animation Quiz 4 - Addition and Deletion Mutations

Huntington’s Disease: the sequence C-A-G is inserted up to 100 times into a normal gene, messes up the reading of the normal genetic code, causing abnormal protein production or a lack of protein production. Huntington’s Disease: the sequence C-A-G is inserted up to 100 times into a normal gene, messes up the reading of the normal genetic code, causing abnormal protein production or a lack of protein production. Causes nervous system degeneration Causes nervous system degeneration Neurofibromatosis: Neurofibromatosis: insertion of DNA sequences that do not code for anything right into the middle of the DNA sequences that do code for certain proteins.

Chromosomal Alterations/mutations: Gross alterations that affect the structure and/or the number of chromosomes. These include: a) Translocation b) Nondisjunction: chromatids fail to split at centromere (Turner’s syndrome) c) Duplication d) Inversion e) Deletion

Cystic fibrosis: caused by deletion on chromosome 7. Causes the lungs to continually fill with thick mucus, which can contain bacteria and cause pneumonia. Cystic fibrosis: caused by deletion on chromosome 7. Causes the lungs to continually fill with thick mucus, which can contain bacteria and cause pneumonia. Duchenne muscular dystrophy: gradual muscle deterioration Duchenne muscular dystrophy: gradual muscle deterioration

What effect can aneuploidy have?

DNA Mutation Problem Set Given the following sequence, what would happen if… DNA: TATATTAGAGGCTCATAT 1 CTTCCTACG 2 TTCTAGAT 3 GTTCTC 4 ATT mRNA: _______________________________ a.a.’s: ________________________________ a) Replace T 3 with A b) Replace GT with CA c) Replace G 2 with A d) A inserted after T 1 e) Remove C 4 Use a separate sheet of paper to solve this problem. Write out the entire mRNA sequence, then the entire sequence of amino acids starting with the start codon. Then replace the bases as indicated and figure out what kind of mutation will occur with each substitution or deletion/insertion.