MUTATIONS

WHAT ARE MUTATIONS? KEY CONCEPT: Mutations are changes in genetic material. VOCABULARY: Mutation, point mutation, frameshift mutation, polyploidy

What happens when a protein malfunctions? If a protein can't do its job, then cells containing that protein may not function properly. Since humans are composed of cells, a malfunction may lead to medical problems.

HOW DO MUTATIONS HAPPEN? There are two ways in which DNA can become mutated: 1. Mutations can be inherited. This means that if a parent has a mutation in his or her DNA, then the mutation is passed on to his or her children. 2. Mutations can be acquired. This happens when environmental agents damage DNA, or when mistakes occur when a cell copies its DNA prior to cell division.

Here's another way to think about it! Think of a cell as a car. A car is made up of many parts, just as a cell is made up of many proteins. Each part -- or protein -- does a specific job.

ANALOGY What happens when a part breaks on your car? It depends! If one headlight burns out, you can still drive the car, although driving at night may be tough.

ANALOGY Proteins in cells work the same way. Some proteins are more important to a cell's normal function than others. A cell might still be able to function properly if the mutated protein isn't that important, like the headlight on your car.

ANALOGY But when your brakes fail, you're really in trouble -- before you know it, your car is cruising out of control! And if you're driving in traffic when this happens, then your car troubles are certain to affect the cars around you, making problems for the whole street.

KINDS OF MUTATIONS MICROMUTATIONS: Gene mutations result from changes in a single gene.

KINDS OF MUTATIONS 2. MACROMUTATIONS: Chromosomal mutations involve changes in whole chromosomes.

MICROMUTATIONS OR GENE MUTATIONS Point Mutations Affect one nucleotide Occur at a single point in the gene sequence Three Types: Substitution Insertion Deletion

Point Mutations Substitution A single nucleotide is changed in the nucleotide sequence. This may result in a change to a single amino acid in the protein. The change to a single amino acid may or may not alter the proteins function.

Point Mutations - Substitution Codon = Amino Acid UGU Original Cysteine UGC No Change UGG Single AA Tryptophan UGA Bad STOP

GENE MUTATION: SUBSTITUTION DNA: TAC GCA TGG ATT mRNA: AUG CGU ACC UUA Amino Acid: MET ARG THR LEU Substitution DNA: TAC GTA TGG ATT mRNA: AUG CGU ACC UUA Amino Acid: MET HIS THR LEU

Substitution Mutations Transition 3’AGTTCAG-TAC-TGA-ACA-CCA-TCA-ACT-GATCATC5’ 5’AGUC-AUG-ACU-UGU-GGU-AGU-UGA-CUAGAAA3’ Met Thr Cys Gly Ser Pyrimidine to Pyrimidine 3’AGTTCAG-TAC-TGA-ATA-CCA-TCA-ACT-GATCATC5’ 5’AGUC-AUG-ACU-UAU-GGU-AGU-UGA-CUAGAAA3’ Met Thr Gly Ser Tyr Transversion 3’AGTTCAG-TAC-TGA-ACA-CCA-TCA-ACT-GATCATC5’ 5’AGUC-AUG-ACU-UGU-GGU-AGU-UGA-CUAGAAA3’ Met Thr Cys Gly Ser Purine to Pyrimidine 3’AGTTCAG-TAC-TGA-AAA-CCA-TCA-ACT-GATCATC5’ 5’AGUC-AUG-ACU-UUU-GGU-AGU-UGA-CUAGAAA3’ Met Thr Gly Ser Phe

Insertions & Deletions Point Mutations Frameshift Mutations Result From Insertions & Deletions A nucleotide is added, or subtracted from the nucleotide sequence. This shifts the Codon grouping and drastically alters the amino acid sequence in the protein.

GENE MUTATION: INSERTION DNA: TAC GCA TGG ATT mRNA: AUG CGU ACC UUA Amino Acid: MET ARG THR LEU Insertion DNA: TAT CGC ATG GAA T mRNA: AUA GCG UAC CUU A Amino Acid: ILE ALA TRY LEU

GENE MUTATION: DELETION THE FAT CAT ATE THE RAT Deletion THE F AT C AT A TE T HE R AT AT TEF ATC ATA TET HER The loss of a single DNA base can change the entire message that DNA sends to make a protein! DIFFERENT DNA MESSAGE = DIFFERENT PROTEIN

Frame Shift Mutations 3’AGTTCAG-TAC-TGA-ACA-CCA-TCA-ACT-GATCATC5’ 3’AGTTCAG-TAC-TGA-AAC-CAT-CAA-CTG-ATCATC5’ 3’AGTTCAG-TAC-TGA-ACA-CCA-TCA-ACT-GATCATC5’ 5’AGUC-AUG-ACU-UGU-GGU-AGU-UGA-CUAGAAA3’ Met Thr Cys Gly Ser 5’AGUC-AUG-ACU-UUG-GUA-GUU-GAC-UAG-AAA3’ Met Thr Val Leu Frame shift mutations tend to have a dramatic effect on proteins as all codons down stream from the mutation are changed and thus code for different amino acids. As a result of the frame shift, the length of the polypeptide may also be changed as a stop codon will probably come at a different spot than the original stop codon.

MACROMUTATIONS: CHROMOSOMAL MUTATIONS Changes the number or structure of chromosomes As a result the locations of genes on chromosome or the number of copies of some genes may change.

MACROMUATIONS: CHROMOSOMAL MUTATIONS 1 Deletions - Loss of chromosome sections 2 Duplications - Duplication of chromosome sections 3 Inversions - Flipping of parts of chromosomes 4 Translocations - Movement of one part of a chromosome to another part

MACROMUTATION: DELETION X Deletion Loss of all or part of a chromosome

MACROMUTATION: DELETION Original chromosome Centromere A B C D E F G H Genes A B C D G H New Chromosome E F

MACROMUTATION DUPLICATION Segment of chromosome is repeated

MACROMUTATION: DUPLICATION Original chromosome Centromere A B C D E F G H Genes E F Duplication New Chromosome A B C D E F E F G H

MACROMUTATION: INVERSION Chromosome or part of a chromosome is placed in the reverse direction

MACROMUATION: INVERSION Original chromosome Centromere Genes A B C D E F G H Inversion New chromosome A B C D F E G H

MACROMUTATION: TRANSLOCATION Part of one chromosome breaks off and attaches to another chromosome

MACROMUTATION: TRANSLOCATION Original Chromosome Centromere Genes A B C D E F G H New chromosome A B E F C D G H

SIGNIFICANCE OF MUTATIONS Most mutations are NEUTRAL— they have little or no effect on genes or the function of proteins. We all have mutations within our DNA

HARMFUL MUTATIONS Mutations can cause a dramatic changes in the protein structure are often HARMFUL. THESE DEFECTIVE PROTEINS CAN DISRUPT NORMAL BIOLOGICAL ACTIVITIES. Harmful mutations are associated with many types of cancer.

BENEFICIAL MUTATIONS Mutations are also the source of GENETIC VARIATION in a species. Beneficial mutations may produce proteins with new or altered activities that can be useful to organisms in different or changing environments.

BENEFICIAL MUTATIONS POLYPLOIDY: organism has extra sets of chromosomes When a complete set of chromosomes fail to separate during meiosis, the gametes that result may produce TRIPLOID (3N) or TETRAPLOID (4N) organisms.

BENEFICIAL MUTATIONS Polyploid plants are often larger and stronger than diploid plants. Important crop plants have been produced in this way. Example: bananas, citrus fruits, seedless plants

INHERITED MUTATIONS DNA fails to copy accurately Most of the mutations that we think matter to evolution are "naturally-occurring." For example, when a cell divides, it makes a copy of its DNA — and sometimes the copy is not quite perfect. That small difference from the original DNA sequence is a mutation.

INHERITED MUTATIONS

EXTERNAL INFLUENCES CAUSE MUTATIONS Mutations can be caused by exposure to specific chemicals or radiation. These agents cause the DNA to break down.

EXTERNAL INFLUENCES CAUSE MUTATIONS This is not necessarily unnatural — even in the most isolated and pristine environments, DNA breaks down. Nevertheless, when the cell repairs the DNA, it might not do a perfect job of the repair. So the cell would end up with DNA slightly different than the original DNA and hence, a mutation.