Mutation Three CAUSES: Definition: Is a permanent change in DNA. Organism changes as a result of the change in gene structure Three CAUSES: 1. Spontaneous errors in DNA replication: nucleotides lost, rearranged, paired incorrectly 2. Mutagens: Are anything that interacts with DNA (internal or external factors) that cause an increased rate of mutation 3. Transposons: DNA sequence capable of randomly moving from one site to another in another in the genome

Mutagens – 3 types: a) Chemical mutagens: e.g. dioxins, benzene, asbestos, DDT, cigarette smoke, pesticides, manufactured chemicals b) Radioactive Mutagens: e.g. UV rays, X-rays. Note: some may be natural (e.g. sun) e.g. bacteria and viruses. Human pampiloma virus (HPV) causes warts; Hepatitis B and C cause liver damage and cancer c) Biological Mutagens: Exposure to mutagens especially dangerous for pregnant women – embryo growing rapidly; few embryonic cells give many adult cells.

Gene Mutations Where can mutations occur? Somatic (body) cells: Disrupts normal cell function. Affects individual, but not passed onto offspring. E.g. many cancers   Gamete (sex) cells: Mutations are transmitted to offspring, can change a population’s gene pool (and evolution)

Types of Gene Mutations Point Mutations: = simplest; is a change in just ONE base pair in a single gene. A point mutation can occur as a: A nucleotide substitution, Missense With varying results   Frameshift Mutations: = Involves an Insertion or Deletion With more severe results

Mutations Impacts to DNA using an English Sentence Analogy: Original Strand: BIG DOG BIT TED   a) Substitution: BIG JOG BIT TED One nucleotide is substituted for another. E.g CCT => CCG. This may or may not change the amino acid. b) Addition: BIG DOG BBI TTE D One nucleotide is added – the reading frame is shifted . All nucleotides are changed after. SERIOUS c) Deletion: IGD OGB ITT ED One nucleotide is deleted – all the codons are changed from the point of the deletion. SERIOUS

Point Mutations Point Mutations can be : -Silent: -Missense:   -Silent: DNA=ACA→ACG, mRNA=UGU→UGC, AA=Cys →Cys -Missense: DNA=ACA→ACC, mRNA=UGU→UGG, AA= Cys→ Trp When a point or frameshift mutation changes a codon within a gene into a stop codon, translation will be altered into a: -Nonsense: DNA=ACA→ACT, mRNA=UGU→UGA, AA=Cys→STOP

Genetic Mutations Original Strand:   Addition: Substitution:

Genetic Disorders Sickle Cell Anemia: Phenylketonuria (PKU): Albinism: - valine replaces glutamate in amino acid chain of hemoglobin   - normal blood cells replaced by sickle shaped cells - abnormal cells block blood vessels, normal cells cannot get through, tissue starved of oxygen, nutrients Phenylketonuria (PKU): - tyrosine converted to phenylpyruvic acid - acid build up causes nervous system damage, mental slowness Albinism: - enzyme that converts tyrosine to melanin defective - subjects will have no skin/hair pigment, appear almost pure white

Chromosomal Mutations Inversion Translocation   Duplication Deletion

Chromosomal Disorders Down's Syndrome: - extra chromosome #21   facial features change, slower mental processing Turner's Syndrome: - absence of second X or Y chromosome - person is single X – short infertile female Kleinfelter's Syndrome: - 3 sex chromosomes – XXY - person is a male that grows tall with long limbs, generally have IQ’s significantly below siblings - sperm count may be reduced or person may be infertile