Mutations

1. Because Stuff Happens Mutations

2. A. Mutation Overview • Any change or random error in the nucleotide sequence (either DNA or mRNA) is called a mutation • Can occur in any cell in body • Gamete (sex cell): cell that determines sex; sperm or egg cell in animals; pollen or ovules in plants • Mutation passed down to offspring • Somatic (body) cell: all other cells • Mutation stays with cell; may be copied in cell replication

3. Skin cancer is not inherited because it occurs in somatic or body cells

5. Two types of mutations: • Point mutation: one base is mutated into another (one amino acid change) • Frameshift mutation: one base is added or deleted (all amino acids changed) • Affects may be neutral (no change in expression or protein made), positive, or negative (disease or death)

6. A mutation in the thumb joint changed it to an opposable thumb = positive mutation!

7. Introns & Exons • Entire DNA strand is 3 billion (3,000,000,000) base pairs • In eukaryotes, divided into two types: • Introns: no coding information (nonsense) • Exons: code for proteins

8. Why would eukaryotic DNA have so many nonsense base pairs or “junk?” • Protection – mutation here wouldn’t harm protein (neutral mutation) mutation INTRON EXON INTRON

9. Before mRNA leaves nucleus - therefore before translation (making proteins from mRNA) - introns must get cut out by process called splicing • Done by specific enzymes called spliceosomes

10. Point Mutation • Single nucleotide (base, PO4, sugar) changes • Original : The fat cat ate the wee rat. • Mutation: The fat hat ate the wee rat. • Many diseases are result of single point mutation in gene • Sickle-cell anemia • Cystic fibrosis

12. Sickle cell anemia • Point mutation: aa glutamine mutated into valine • Result: red blood cell changed from round shape to sickle (crescent) shape • Gets stuck on walls of blood vessels & can cause clog

13. Cystic fibrosis • Point mutation: aa glutamine becomes STOP codon • Result: should be 1480 aa in protein, now only 493 • Mucosal cells produce excess mucus which blocks ducts (tubes linking organs) which causes infections

14. Frameshift • Any mutation which causes shift of codon sequences or incorrect amino acid number • Caused by two scenarios: • Deletion of nucleotide (base) • Original: The fat cat ate the wee rat. • Mutation: The fat atatet hew eer at. • Insertion of extra nucleotide(s) (base) • Original: The fat cat ate the wee rat. • Mutation: The fat caa tat eth ewe era t.

15. Frameshift

16. Many diseases caused by frame-shift mutations • Huntington’s disease • Fragile X Syndrome • Muscular Dystrophy • Tay-Sachs disease

17. Huntington’s Disease • Mutation: additional CAG in protein • Result: early cell death in brain Huntington’s Disease Normal

18. Fragile X Syndrome • Mutation: extra GGG codons inserted on X chromosome • Result: intellectual disability in males normal

19. Muscular dystrophy • Mutation: extra CTG or CCTG in muscle protein • Result: deteriorating (weakening) muscles

20. Tay-Sachs Disease • Mutation: insertion of TACT in exon 11 • Result: enzyme that breaks down fat in central nervous system (brain & spinal cord) defective • Fat accumulates on brain & spinal cord, permanently damaging cells & killing child before age 5

22. Point vs. Frameshift