Because Stuff Happens Mutations

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: cell that determines sex; sperm or egg cell Mutation passed down to offspring Somatic cell: all other cells Mutation stays with cell; may be copied in cell replication

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

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), positive, or negative (disease or death)

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

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

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

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

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 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

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

Frameshift Deletion of nucleotide (base) 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 ata tet hew eer at. Insertion of extra nucleotide(s) (base) Mutation: The fat caa tat eth ewe era t. Many diseases caused by frame-shift mutations

Frameshift

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

Mutation: extra GGG codons inserted on X chromosome Fragile X Syndrome Mutation: extra GGG codons inserted on X chromosome Result: mental retardation in males normal

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

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

Point vs. Frameshift

Classwork Mutations worksheet Use mRNA codes to look up amino acids in proteins Do the same thing for the mutated mRNAs. a. Where is the mutation? Either circle it or explain (G is now C or G got deleted/inserted) b. What is the result? Describe the change to the amino acid(s) .

Homework Do p. 220 #3-5 Do p. 222 #1-3, 8, 10-12 Study for a quiz tomorrow just on central dogma (25 points) Transcription – DNA to RNA Translation – RNA to protein Know the process of transcription and translation (how it happens, where it happens, what happens)