gene mutations
DESCRIPTION
Gene Mutations. Mutation Vocabulary. Gene Mutation. Chromosomal Mutation. Duplication Deletion Translocation Inversion. Point Mutation Substitution Silent Missense Nonsense Frameshift Insertion Deletion. Chromosomal Mutations. How do genes control metabolism. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/1.jpg)
Gene Mutations
![Page 2: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/2.jpg)
Mutation Vocabulary
Gene Mutation• Point Mutation
– Substitution– Silent– Missense– Nonsense
• Frameshift– Insertion– Deletion
Chromosomal Mutation• Duplication • Deletion• Translocation• Inversion
![Page 3: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/3.jpg)
Chromosomal Mutations
![Page 4: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/4.jpg)
How do genes control metabolism
• In 1909, Archibald Garrod first proposed the relationship between genes and proteins.
• “Genes dictate phenotypes through enzymes that catalyze specific chemical processes in the cell.”
• Example: Alkaptonuria – Urine appears dark red because it contains alkapton, that darkens upon exposure to air. – Wild Type Individuals have an enzyme to break the chemical
down.– Mutant Individuals do not produce the enzyme, thus unable
to metabolize alkapton.
![Page 5: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/5.jpg)
![Page 6: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/6.jpg)
Beadle and Tatum
One Gene – One Enzyme hypothesis : the Function of one gene is to dictate the production of a specific enzyme.
![Page 7: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/7.jpg)
Transcription in Prokaryotes
• RNA polymerase cannot initiate transcription on its own. A protein (sigma) must bind before transcription can begin.
• RNA Polymerase + Sigma = HOLOENZYME • When a holoenzyme + DNA mix, the enzyme will attach to
only specific regions on the DNA which they now refer to as PROMOTERS. Specifically positions 10 and 35 nucleotides upstream from the gene.
• The sigma appeared to be responsible for guiding the RNA polymerase to specific locations.
• The sigma will release once initiation has commenced.
![Page 8: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/8.jpg)
![Page 9: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/9.jpg)
Promoter Sequence• 20 – 25 base pairs long. • Similar segment of DNA had a series of bases
identical or similar to TATAAT. – Referred to as the – 10 box.
![Page 10: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/10.jpg)
Translation in Prokaryotes
• A large and small subunit assemble onto the mRNA. The small subunit will attach to what is called the Shine-Dalgarno Sequence on the mRNA. – A 6 base sequence upstream 8 bases from the AUG
start codon. The rRNA sequence within the small subunit will attach.
– Shine-Dalgarno Sequence – AGGAGG– Anti Shine-Dalgarno Sequence (found on the
ribosome) - UCCUCC
![Page 11: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/11.jpg)
Translation in Prokaryotes
• The large subunit will attach and attract the first tRNA molecule. Loading in at the P-site of the ribosome.
![Page 12: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/12.jpg)
Repairing Mistakes in DNA Synthesis
• Replication forks work at 50 bases per second• Errors = one mistake per billion• HUMAN REPLICATION– 6 billion nucleotides– Cells are replicated to create trillions of cells
![Page 13: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/13.jpg)
DNA Polymerase Proofreading in Prokaryotes
• DNA polymerase acts as an exonuclease – (an enzyme that removes nucleotides from DNA)
• DNA polymerase III can remove nucleotides only from the 3’ end of the DNA, and only if they are not hydrogen bonded to a base on the complementary strand.
• If a wrong base is added during DNA synthesis, the enzyme pauses, removes the mismatched base that was just added, and then proceeds with synthesis.
![Page 14: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/14.jpg)
Eukaryotic DNA polymerases
• Have the same type of proofreading ability – reduces error rate to about 1 in 10 million bases.
• At this rate there would be 600 mistakes every time a human cell replicated
![Page 15: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/15.jpg)
Three Types of DNA Repair
• 1. Mismatch Repair• 2. Thymine Dimer Repair• 3. Excision Repair
![Page 16: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/16.jpg)
Mismatch Repair
• When DNA polymerase doesn’t fix the problem, other enzymes spring into action. Responsible for “mismatch repair”
• The first repair enzyme is known as mutS.• “mutatorS”
![Page 17: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/17.jpg)
Which base is right?
• Hypothesis: At the conclusion of a replication process, a methyl group is added. So the proofreading enzyme will remove the nucleotide from the unmethylated strand.
![Page 18: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/18.jpg)
Xeroderma Pigmentosum: A Case Study (DNA Repair Disorder)
• An autosomal recessive disease in humans. • Extreme sensitivity to UV light. Skin will develop
leasion after even slight exposure to sunlight. • UV Light will cause a covalent bond to form
between adjacent Thymines on a DNA strand. • Creates a kink in the secondary structure of DNA. • Causes a stall in the replication fork during
replication.
![Page 19: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/19.jpg)
![Page 20: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/20.jpg)
The Study
• Cells of “normal” individuals versus cells of XP individuals.
• Exposed cells to UV radiation.• Added radioactive Thymines to the cell which
should be incorporated IF repair occurs. • High amount of radioactive Thymines in the
normal and virtual no radioactive thymines in the XP individuals.
![Page 21: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/21.jpg)
DNA Excision Repair
• Uvr A, Uvr B, Uvr C, and Uvr D– “Ultraviolet Light Repair”
![Page 22: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/22.jpg)
![Page 23: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/23.jpg)
Direct DNA repair
DNA photolyase
![Page 24: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/24.jpg)
DNA Mismatch Repair and Cancer(DNA Repair Disorder)
• Colon Cancer Variation = Hereditary nonpolyposis colorectal cancer (HNPCC) runs in families
• Tumors will develop on the colon, ovary, and other organs by the age of 50
• 1990 – researchers mapped the susceptibility to an area on chromosome 2
![Page 25: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/25.jpg)
Do humans have mismatch repair genes?
• The research accelerated when mutS gene was identified and then research found a similar gene in a yeast genome.
• The genes were so similar, they called them homologous.
• Using the sequences from the genes, they located a similar sequence in the human gene – known as hMSH (human mutS homolog)
• Mapped to the same region on chromosome 2 as the HNPCC susceptibility gene.
![Page 26: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/26.jpg)
Link between cancer and mismatch repair
• Cells from these patients have a mutation rate 100 times the normal.
• People who inherit a nonfunctional copy of the hMSH gene have a genetic predisposition for developing HNPCC.
• Evidence: Individuals who have this form of colon cancer have uneven repeats of sequences in their DNA (usually fixed in DNA repair).
![Page 27: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/27.jpg)
Ataxia Telangiectasis (AT)
• Defect in the enzyme KINASE. • Cells proceed through the checkpoints. (high
mutation rate)• Radiation Sensitivity– Increased risk of breast cancer. – Any problems?
![Page 28: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/28.jpg)
![Page 29: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/29.jpg)
Potential Benefits to this research
• If individuals with mutant forms of hMSH can be identified early in life, dietary changes and therapy could significantly reduce their risk of developing cancer
![Page 30: Gene Mutations](https://reader035.vdocument.in/reader035/viewer/2022062321/568138a0550346895da05e63/html5/thumbnails/30.jpg)
Semi-conservative Replication
• Meselson and Stahl Experiment