1. From Gene to Protein: Translation & Mutations
Chapter

2. Recall: Central dogma of molecular biology Steps of gene expression
DNA RNA  Protein
Steps of gene expression
Transcription, RNA processing (eukaryotes), Translation

3. 17.4
Translation is the RNA-directed synthesis of a polypeptide

4. Translation Components necessary: tRNA Ribosome
Made of RNA and protein subunits
Larger in eukaryotes
Anatomy:
P site – holds tRNA carrying growing peptide
A site – holds tRNA carrying next a.a. in chain
E site – exit site for discharged tRNA

5. Prokaryotes vs. Eukaryotes
Transcription and translation coupled in prokaryotes
Happen simultaneously
DNA is already in cytoplasm
Transcription and translation are separate in eukaryotes
DNA is in nucleus, ribosomes in cytoplasm
mRNA must be edited first

6. Translation: Initiation
mRNA binds to the ribosome
Initiator tRNA binds to start codon on mRNA (AUG)
1st a.a. = methionine
Large ribosomal subunit binds to complex

8. Translation: Elongation
tRNAs bring in appropriate amino acid to growing chain based on mRNA codon
This process continues until a stop codon is reached (UGA, UAA, UAG)

10. Translation: Termination
Peptide synthesis continues until a stop codon is reached
Peptide is released
Where peptide goes depends on its role

12. The Genetic Code Made of 3 letter codes: codons (found on mRNA)
Table is used to determine which amino acid each codon codes for
It is the same in almost all organisms
Redundant: more than one codon for some AA’s

13. Transcription & Translation Summary

14. 17.5
Mutations of one or a few nucleotides can affect protein structure and function

15. When Protein Synthesis Goes Wrong: Gene Mutations
Changes to the DNA sequence resulting in production of malfunctioning or nonfunctioning protein.
Differ from chromosomal mutations since only single nucleotides are affected.

16. Types of Gene Mutations
Substitution: wrong nucleotide in place
Silent – doesn’t change amino acid, protein
Missense – changes amino acid, protein
Nonsense – changes amino acid to stop codon
Insertion or deletion: nucleotide added or removed
Frameshift

17. Substitution: Sickle Cell Anemia
Caused by a single nucleotide substitution in one of the polypeptides that makes up hemoglobin (Hgb)
Hgb folds incorrectly, causing RBC’s to become sickle shaped
They cannot carry O2 as effectively

18. Deletion: Cystic Fibrosis
Most common mutation that causes CF is the result of a deletion in CFTR gene
Mutation causes faulty CFTR protein
This protein transports Cl- ions across cell membrane
Causes mucus buildup in lungs, digestive tract

19. Insertion: Huntington’s Disease
Caused by a CAG repeat
Normal Huntington gene: repeats
Mutant gene: >27 repeats
Autosomal dominant
Causes nervous system degeneration leading to loss of motor function, dementia

20. Not all mutations are harmful…
Increase variation, drives evolution
Example: gene duplication
“Antifreeze” fish (Antarctic toothfish, Arctic cod)
Can survive ocean waters below freezing (-2°C)
How?
Multiple copies of a gene that normally codes for a pancreatic digestive protein were copied.
These duplicated bits of the genome, now no longer used in digestion, experienced natural selection that shaped them to aid survival in lower temperatures.
Eventually, this ancient gene evolved into the modern day gene that codes for the fish's antifreeze glycoproteins.

21. 17.6
While gene expression differs among the domains of life, the concept of a gene is universal