Transcript Lecture 11 Biol302 Spring 2012

Evolution?
The Molecular Basis of
Mutation-Evolution
Mutations alter the nucleotide sequences of genes in
several ways, for example the substitution of one base
pair for another or the deletion or addition or one or a
few base pairs.
Tautomeric Shifts
Tautomeric Shifts Affect
Base-Pairing
Mutation Caused by
Tautomeric Shifts
Base Substitutions
A transition replaces a pyrimidine with another
pyrimidine or a purine for another purine.
A transversion replaces a pyrimidine with a
purine or a purine with a pyrimidine.
Previously discussed
Frameshift Mutations
Factors Influencing the Rate
of Spontaneous Mutations
Accuracy of the DNA replication
machinery
Efficiency of the mechanisms for the
repair of damaged DNA
Degree of exposure to mutagenic
agents in the environment
Induced Mutations
 Induced mutations occur upon exposure to physical
or chemical mutagens.
 Hermann J. Muller and Edgar Alternburg measured
the frequency of X-linked recessive lethal mutations
in Drosophila.
 Muller demonstrated that exposing Drosophila sperm
to X-rays increased the mutation frequency.
Chemical Mutagens
Types of Chemical Mutagens
Chemicals that are mutagenic to both
replicating and nonreplicating DNA
(e.g., alkylating agents and nitrous acid)
Chemicals that are mutagenic only to
replicating DNA (e.g., base analogs and
acridine dyes)
A Base Analog:
5-Bromouracil…it is more like
Thymine!
Mutagenic
Effects of 5Bromouracil
Nitrous Acid Causes Oxidative
Deamination of Bases
Intercalation of an Acridine Dye
Causes Frameshift Mutations
Alkylating Agents
 Alkylating agents are chemicals that donate alkyl groups
to other molecules.
 Alkylating agents induce transitions, transversions,
frameshifts, and chromosome aberrations.
 Alkylating of bases can change base-pairing properties.
 Alkylating agents can also activate error-prone DNA
repair processes.
Hydroxylamine
Hydroxylamine is a hydroxylating agent.
Hydroxylamine hydroxylates the amino
group of cytosine and leads to G:C
A:T transitions.
The Electromagnetic Spectrum
X-rays induce mutations through ionization.
Ultraviolet light induces mutations through
excitation- Energy addition.
Irradiation Dosage and
Mutation Frequency
Ionizing Radiation Causes Changes
in Chromosome Structure
Ionizing radiation breaks chromosomes
and can cause deletions, duplications,
inversions, and translocations.
These types of mutations display twohit kinetics.
Thymine Dimers
Mutagenesis by Ultraviolet Irradiation
 Hydrolysis of cytosine to a
hydrate may cause
mispairing during replication
 Cross-linking of adjacent
thymine forms thymidine
dimers, which block DNA
replication and activate
error-prone DNA repair
mechanisms.
Mutations Induced by Transposons
Wrinkled Pea
Previously discussed
Expansion of Trinucleotide Repeats
 Simple tandem repeats are repeated sequence of
one to six nucleotide pairs.
 Trinucleotide repeats can increase in copy number
and cause inherited diseases.
 Examples: Fragile X Syndrome, Huntington disease,
spinocerebellar ataxia
 These diseases are characterized by anticipation,
the increased severity of disease or earlier age of
onset in successive generations as the trinucleotide
copy number increases.

Mutations are induced by chemicals, ionizing irradiation,
ultraviolet light, and endogenous transposable genetic
elements.

Point mutations are of three types:
(1)
(2)
(3)
Transitions—purine for purine and pyrimidine for pyrimidine
substitutions,
Transversions—purine for pyrimidine and pyrimidine for purine
substitutions, and
Frameshift mutations—additions or deletions of one or two
nucleotide pairs, which alter the reading frame of the gene distal
to the site of the mutation.
You must know for your future
Evolution?
Alpha and Beta chain mutants…some of them
Phylogenetic relationships
How could we use GFP fluorescence
to figure out-codon optimize GFP?