1. FROM GENE TO PROTEIN: TRANSLATION & MUTATIONS Chapter 17.4-17.6

2. Recall: Central dogma of molecular biology 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: 1. tRNA 2. 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 O 2 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: 10-26 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