Gene Mutation, DNA Repair, and Transposition

Mutation

Change in a DNA sequence.

Mutation

Any base-pair change in any part of DNA molecules can be considered as this.

Loss and Gain Function Mutation

Classification based on Phenotypic Effects

Loss of Function Mutation

Eliminates the function of the gene product.

Null Mutation

Any type of mutation that can lead to a loss of a function.

Gain of Function Mutation

Results in gene products with a new function due to change in the amino acid sequence.

Germline Mutation

Change occurs during the DNA replication that precedes meiosis.

Germline Mutation

Transmitted to the next generation of individuals.

Somatic Mutation

Happens during DNA replication before a mitotic cell division.

Somatic Mutation

Affects only cells that descend from changed cell.

Clinical Applications

Identifying how mutations causes symptoms.

Beta Globin and Collagen Genes

Examples of mutations that cause disease.

Mutations

May occur spontaneously or by exposure to chemical or radiation.

Mutagen

An agents that causes a mutation.

Spontaneous Mutation

De novo or new mutations.

Spontaneous Mutation

Not caused by exposure to known mutagen.

Spontaneous Mutation

Result from errors in DNA replication.

Spontaneous Mutation

DNA bases have slight chemical instability.

Spontaneous Mutation Rate

Differs between genes.

Larger Genes

Usually have higher mutation rates.

Multiple new mutations

Each individual has this

Mitochondrial Genes

Mutate at a higher rate than nuclear genes because they cannot repair their DNA.

Mutational Hot Spots

In some genes, mutations are more likely to occur in regions.

Short Repetitive Sequences

Pairing of repeats may interfere with replication or repair enzymes.

Palindromes

Often associated with insertions or deletions.

Induced Mutations

Caused by mutagens, many are also carcinogens and cause cancer.

Alkylating Agents

Remove a base

Acridine Dyes

Add or remove base

X rays

Break chromosomes

UV radiation

Creates thymine dimers

Site-Directed Mutagenesis

Changes a gene in a desired way.

Ames Test

An in vitro test of the mutagenicity of a substance.

Salmonella Bacteria

A version of Ames Test with mutation gene for histidine.

Bacteria

Exposed to the text substance.

Bacteria

Only grow if mutations have occurred.

Unintentional mutagen exposure

Workplace, industrial accidents (chernobyl), medical treatments, weapons, and natural sources (cosmic rays, sunlight, and earth’s crust)

Mutations

Is classified by whether they remove, alter, or add a function and by exactly how they structurally alter DNA.

Transition

Purine replaces purine or pyrimidine replaces pyrimidine.

Transversion

Purine replaces pyrimidine or pyrimidine replaces purine.

Missense Mutation

Replaces one amino acid with another.

Nonsense Mutation

Changes a codon for an amino acid into a stop codon. Creates truncated proteins that are often non-functional.

Stop Codon

Changed to a coding codon lengthens the protein.

Intron

Alters a site when it is normally removed from mRNA.

Can affect the phenotype

Intron is translated or exon is skipped.

Intron

Translated

Translated

Intron

Exon

Skipped

Skipped

Exon

Genetic Code

Read in triplets

Nucleotides

Changes not in multiples of 3 lead to disruptions of the reading frame.

Frameshift Mutation

Alter amino acids after mutation.

Nucleotide

Changes in multiples of 3 will not cause a frame-shift.

Nucleotide

Can still alter the phenotype.

Deletion

Removes genetic material.

Insertion

Adds genetic material

Tandem Duplication

An insertion of identical sequences side by side.

Pseudogenes

A DNA sequence similar to a gene but which is not translated.

Pseudogenes

May have evolved from original gene by duplication and acquired mutation.

Pseudogene and Functional Gene

The crossing over between these can disrupt gene expression.

Silent Mutations

Mutations that do not alter the encoded amino acid.

Synonymous Codons

A mutation from CAA to CAG alters the DNA, but the protein sequence remains unchanged.

CAA and CAG

Code for glutamine.

Missense Mutation

Alters the encoded amino acid to another amino acid.

Missense Mutation

Creates a nonsynonymous codon.

Nonsynonymous Mutations

Are conservative that encode a chemically similar amino acid and may not alter function.

Missense Mutation

Its impact is not predictable from protein sequence alone.

Conditional Mutation

Produces a phenotype under particular conditions or environments.

Glucose 6-phosphate dehydrogenase enzyme

Responds to oxidants, chemicals that strip electrons from other molecules.

High levels of oxidants

Occur when eating fava beans or taking certain antimalarial drugs.

DNA Repair

Errors in DNA replication or damage to DNA create mutations.

Photoreactivation, Excision, Mismatch

Types of DNA Repair

Photoreactivation Repair

Enzymes called photolyases use light energy to break the extra bonds in a pyrimidine dimer.

Photoreactivation Repair

Enables UV-damaged fungi to recover from exposure to sunlight.

Photoreactivation Repair

Humans do not have this type of repair.

Photolyases

Enzymes that uses light energy to break the extra bonds in a pyrimidine dimer.

Excision Repair

Pyrimidine dimers and surrounding bases are removed and replaced.

Nucleotide and Base

Humans have two types of excision repair.

Nucleotide Excision Repair

Replaces up to 30 bases, corrects mutations caused by different insults.

Base Excision Repair

Replaces 1-5 bases, specific to oxidative damge.

Mismatch Repair

Enzymes detect nucleotides that do not base pair in newly replicated DNA. The incorrect base is excised and replaced.

Enzymes

Detect nucleotides that do not base pair in newly replicated DNA.

Proofreading

The detection of mismatches.

Protein p53

Monitors repair of DNA

Apoptosis

If damage is too sever, the p53 protein promotes programmed cell death.

Transposable Elements

Also knows as transposons or jumping genes.

Transposable Elements

They move within the genome and may disrupt genetic function.