BSC 219

Mutation and DNA Repair

11/1/12

18.1 Mutations Are Inherited Alterations in the DNA Sequence

The Importance of Mutations

Source of all genetic variation, which further provides the raw material for evolution

Source of many diseases and disorders

Useful for probing fundamental biological processes

Categories of Mutations

Somatic mutations-occur in “body” of organism. Result in mosaic pattern of cells, but not passed down.

Germ-line mutations-occur in cells producing gametes. Mutation is typically passed to half of offspring.

Types of Gene Mutations (based on their molecular nature)

Base substitutions

Transition-Pu for Pu; Py for Py

Transversion-Pu for Py; Py for Pu

Insertions and deletions

Frameshift mutations-disrupts codon pattern

In-frame insertions and deletions-insert or delete number of bases that is divisible by 3.

Phenotypic Effects of Mutations

Forward mutation: wild type à mutant type

Reverse mutation: mutant type à wild type

Missense mutation-results in a different amino acid at one position of encoded protein

Phenotypic Effects of Mutations

Silent mutation-different codon but still encodes for same amino acid

Neutral mutation-missense mutation that changes amino acid sequence, but does not alter function of protein

Nonsense mutation-changes amino acid into stop thus producing truncated protein

Phenotypic Effects of Mutations

Loss-of-function mutations-cause complete or partial loss of protein function

Gain-of-function mutations-cause either new function or function expressed at new times or location within organism

Conditional mutation-altered function only under certain conditions (temperature sensitive)

Phenotypic Effects of Mutations

Lethal mutation-severe enough to cause premature death

Suppressor mutation: a mutation that hides or suppresses the effect of another mutation

Intragenic-mutation in same gene as original mutation restores function

Intergenic-mutation in other gene restores function (sometimes in tRNA genes)

Phenotypic Effects of Mutations

Mutation rate-the rate at which a mutations occur.

May be determined under normal conditions

May be determined under altered conditions

May be determined in the presence of harmful chemicals

Spontaneous Replication Errors

Caused by mispairing through wobble

Spontaneous Replication Errors

Strand slippage

Unequal crossing over

Depurination: loss of purine

Deamination: loss of an amino group

Chemically Induced Mutations

Mutagen-a compound that induces mutations

Base analogs-modified bases that function similar to regular bases in base pairing events

Chemically Induced Mutations

Alkylating agents: donate alkyl group

Ehtylmethylsulfonate EMS

Mustard gas

Deamination: nitrous acid

Hydroxylamine: add hydroxyl group

Oxidative reaction: superoxide radicals

Hydrogen peroxide

Intercalating agents: proflavin, acridine orange, and ethidium bromide

Radiation

Pyrimidine dimer: two thymine bases block replication.

SOS system in bacteria: SOS system allows bacteria cells to by pass the replication block with a mutation-prone pathway.

18.3 Mutations Are the Focus of Intense Study by Geneticists

The Analysis of Reverse Mutations

Ames Test-test used to determine relative mutagenic ability of a chemical

18.4 A Number of Pathways Repair Changes in DNA

Mismatch Repair

Mismatch-repair enzyme complex

Takes place shortly after replication

Direct repair: photolyase

Modification of altered base to restore

Base-excision repair

Single base is removed

Nucleotide-excision repair

Mismatch Repair

Genetic diseases and faulty DNA repair

Xeroderma pigmentosum