Chapter 7: Anatomy and function of a gene; dissection through mutation

mutation

change in the DNA sequence

forward mutation

changed wild-type allele to a different allele

reverse mutation

changes mutant allele back to wild type

substitution

replacement of a base by another base. There are two types:

- transition

- transversion

transition

purine replaced by another purine or pyrimidine replaced by another pyrimidine

transversion

purine replaced by a pyrimidine, or a pyrimidine replaced by a purine

deletion

block of 1 or more base pairs lost from DNA

insertion

block of 1 or more base pairs added to DNA

mutation rates

- each child contains about 60 mutations that are different from either parent

- most mutations don’t influence phenotype

- male germ cells undergo mitosis continually

- more mutations in sperm from older fathers

s. Luria and M. Delbruck (1943) did a fluctuation test with bacteria to examine its resistance to phage infection. What did the experiment prove?

mutations in bacteria occur spontaneously. They infected wild-type bacteria with phage and saw the majority of cells die, but the cells that remained grew and divided to pass on genes with resistance to phage infection.

types of DNA damage

- depurination 1000/hr in every cell

- deamination of C (removal of NH2 group) to change it to U

- X-rays break the sugar-phosphate backbone of DNA

- UV light causes adjacent thymines to form abnormal covalent bonds (thymine dimers)

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what kind of human diseases are caused by trinucleotide repeats?

- fragile X-syndrome

- Huntington disease

- 18 other diseases

Accurate repair systems

- reversal of DNA alterations (excision pair)

- homology-dependent repair of damaged bases or nucleotides

- correction of DNA replication errors

- double-strand break pair

error-prone repair systems

- SOS system

- microhomology-mediated end-joining (MMEJ)

proofreading function of DNA polymerase

recognizes and exercises mismatches

glycosylases

removes altered nitrogenous bases. Particularly important for removing uracil made from cytosine deamination from DNA and nearby nucleotides. The gap left behind is filled by newly synthesized DNA

UvrA- UvrB complex

scans for distortions to double helix

UvrB- UvrC complex

nicks the damaged DNA

peptide bonds

link amino acid subunits together to form proteins

amino acid structure

- R group that determines type of amino acid

- COOH group and NH2 of adjacent amino acids are joined in covalent peptide bonds

- polypeptides have N terminus and C terminus

the molecular basis of sickle cell anemia

note: sickle-cell anemia is pleotropic (gene functioning in several pathways)

amino acid primary structure

the regular amino acid chain

amino acid secondary structure

characteristic geometry of localized regions (alpha and beta pleated sheets)

amino acid tertiary structure

the complete three-dimensional arrangement of a polypeptide