Unit 4 – Mutations
Every once in a while cells make mistakes in copying
their own DNA, inserting the wrong base or even
skipping a base completely.
These variations are referred to as mutations – from the
Latin mutare (to change).
Mutations are heritable changes in genetic information.
Mutations fall into 2 broad categories:
Gene Mutation – A change to a single gene.
Chromosomal Mutation – A change to a whole
chromosome.
Gene Mutation
Gene mutations that involve changes to one or a
few nucleotide bases as called point mutations
because they occur at a single point in the DNA
sequence.
Point mutations include substitutions, deletions,
and insertions.
Point mutations occur during replication.
If a gene is altered in one cell, the mutation will
carry on in the daughter cells.
Substitutions – in a substitution, one base is
changed to a different base.
Substitutions usually affect no more than a
single amino acid, and sometimes they have no
effect at all.
Example: If a mutation changed one codon of
mRNA from CCC to CCA, the codon would still
specify the amino acid proline.
If, on the other hand, the base change occurred
at the beginning of the codon – ACC instead of
CCC – the resulting amino acid would be
threonine instead of proline.
Insertions and Deletions
Insertions and Deletions are point mutations
where one base is inserted or deleted from a
DNA sequence.
This can have profound differences as DNA
sequences are read three bases at a time during
the production of amino acids.
Insertions and deletions are also referred to as
frameshift mutations – because they shift the
‘reading frame’ of the genetic message.
The alteration of amino acids after the mutation
can alter a protein to the point it no longer
functions as it should.
Chromosomal Mutations
Chromosomal mutations involve changes in the
number or structure of chromosomes.
These mutations can change the location of
genes on chromosomes and can even change the
number of copies of some genes.
There are 4 different types of chromosomal
mutations: deletion, inversion, duplication, and
translocation.
The effects of mutations
Genetic material can be altered either through
natural means, or by artificial means.
The resulting mutations may or may not affect the
organism.
Some mutations that affect individual organisms
can also affect a species or an entire ecosystem.
Many mutations are produced by errors in genetic
processes.
For example, some point mutations result from
errors in DNA replication – one incorrect base gets
inserted per 10 million bases. It is important to
remember these small changes in genes can
accumulate over time. This is the basis for the
evolution of new species 
Mutagens
Some mutations arise from chemical or physical
agents in the environment.
Chemical mutagens include certain pesticides,
plant alkaloids, tobacco smoke, and
environmental pollutants (to name a few).
Physical mutagens include things like some
types of electromagnetic radiation – X-Rays and
UV-A and UV-B light as examples – that interact
with DNA sequences.
Cells can sometimes repair the damage; but
when they can’t. the changes to the DNA
sequences are permanent.
Some compounds interfere with base-pairing
and some weaken the DNA strand itself –
resulting in breaks and inversions that cause
chromosomal mutations.
These compounds are referred to as being
teratogenic.
Examples include:
Alcohol
Tetracycline
Anticonvulsant medications like Dilantin
High doses of Vitamin A
Thalidomide
Rubella
Harmful and Helpful Mutations
The assumption is usually made that mutations
are harmful, or negative.
(Without mutations, species could not evolve)
Most mutations are neutral; they have little or
no effect on the expression of genes or on the
proteins the genes code for.
That being said, let’s look at some harmful
mutations:
Harmful Mutations
Cancer – all cancers result from the mutation of
healthy cells.
Some cancers result from environmental exposure to
carcinogens like asbestos, or smoking related byproducts, or from inherited genetic mutations.
Sickle Cell Anemia – SCA results from a point
mutation in one of the polypeptides found in
hemoglobin. NOTE: Being heterozygous for SCA
confers an advantage to the carrier with respect to
malaria. Being homozygous causes major health
problems and a shortened life span (54 years for
males and 58 years for females)
Beneficial Mutations
Humans have beneficial mutations – ones that
increase bone strength and density, for example.
Plant breeders make good use of ‘good’ mutations –
when a complete set of chromosomes fails to
separate during meiosis, the gametes that result
may produce triploid (3N) or tetraploid (4N)
organisms.
This condition of having extra sets of chromosomes
is called polyploidy.
Polyploid plants are often larger and stronger than
diploid plants.
Important fruit crops like bananas and limes have
been produced this way.
Gene Regulation
Prokaryotic Gene Regulation – Strangely enough,
bacteria and other prokaryotes don’t need to
transcribe all their genes at the same time.
In order to conserve energy and resources,
prokaryotes will use only those genes required for
the cell to function.
By regulating gene expression, bacteria can respond
to changes in their environment.
DNA-binding proteins in prokaryotes regulate genes
by controlling transcription.
One of the keys to gene transcription in bacteria is
the organization of genes into operons. The genes in
the operons are all regulated together, and they
have related functions.
E.coli have 4288 genes (we know this because they
have been mapped) that code for proteins.
A cluster of 3 genes must be turned ‘on’ before the
organism can take advantage of lactose as a food
source.
These 3 genes are called the lac operon. The turning
‘on’ or ‘off ’ of this operon is controlled by proteins
that bind to the DNA and block transcription.
There are 2 regulatory regions on one side of the
operon. The first is called the Promoter (P). This is
the region where RNA binds to begin transcription.
The other region is called the Operator (O) . This is
where the DNA-binding protein that acts as the lac
repressor binds.
Gene regulation in Eukaryotes
• The general principles governing gene
regulation in prokaryotes also apply, with
some exceptions, to eukaryotes.
• One interesting feature is the TATA box. It is a
short region of DNA – roughly 25-30 base
pairs – containing the sequence TATATA or
TATAAA.
• The TATA box binds a protein that assists the
positioning of RNA polymerase by marking a
point just before the beginning of a gene.
• Transcription Factors – Gene expression in
eukaryotic cells can be regulated at a number of
levels.
• One of the most critical is the level of
transcription – by means of DNA-binding proteins
called transcription factors.
• Transcription factors control gene expression by
binding DNA sequences in the regulatory regions
of eukaryotic genes.
• Some transcription factors open up tightly packed
chromatin. Others help attract RNA polymerase,
and others block access to certain genes.
• In most cases, multiple transcription factors must
bind before RNA polymerase is able to attach to
the promoter region and start transcription.
• Promoters have multiple binding sites for
transcription factors, each of which can
influence transcription.
• Certain factors activate scores of genes at
once, altering patterns of gene expression in
the cell.
• Other factors are only formed in response to
chemical signals – like steroids. NOTE: The
factors formed from steroid interaction cause
the activation of multiple genes at the same
time.
RNA interference in gene expression.
• It was discovered by Fire and Mello* that small
pieces of RNA (only a few dozen of bases long)
that are found in cells have two intriguing
characteristics:
1) They are not members of any of the major known
groups of RNA.
2) They play a key role in the regulation of gene
expression by interfering with mRNA. They act
like “sticky tape” by sticking to the mRNA and
preventing the passing on of protein making
instructions.
* Fire and Mello won the Nobel Prize for medicine
in 2006 for this work.