MUTASI

(MUTATION)

The flow of information within a cell involves the transcription

of DNA to mRNA and the translation of mRNA to protein?

The flow of information between cell generations involves DNA

replication and distribution to two equal daughter cells?

A change in DNA to be replicated and passed on to future

generations and to effect protein structure and function if the
change occurred in the gene that coded for that protein?

The cause and effect of changes in DNA?

These changes are called mutations

Mutations

Any change in the DNA sequence of an

organism is a mutation

Mutations are the source of the altered

versions of genes that provide the raw
material for evolution.

Mutations

Most mutations have no effect on the organism,

especially among the eukaryotes, because a large
portion of the DNA is not in genes and thus does not
affect the organisms phenotype.

Of the mutations that do affect the phenotype, the

most common effect of mutations is lethality,
because most genes are necessary for life.

Only a small percentage of mutations causes a visible

but non-lethal change in the phenotype.

Mutations are Random

A central tenet of biology is that the flow of

information from DNA to protein is one way.
DNA cannot be altered in a directed way by
changing the environment. Only random DNA
changes occur.

Types of DNA Change

The simplest mutations are base changes, where one base

is converted to another. These can be classified as
either:
transitions, where one purine is changed to another purine (A

-> G, for example), or one pyrimidine is changed to another

pyrimidine (T -> C, for example).
transversions, where a purine is substituted for a pyrimidine,
or a pyrimidine is substituted for a purine. For example, A -> C.

Another simple type of mutation is the gain or loss one or

a few bases.

Larger mutations include insertion of whole new

sequences, often due to movements of transposable
elements in the DNA or to chromosome changes such as
inversions or translocations.

Deletions of large segments of DNA also occurs.

Types of Mutation
Mutations can be classified according to their effects
on the protein (or mRNA) produced by the gene that is
mutated.

Point Mutations
Frameshift Mutations

Point Mutations

Point mutations are the most common type of mutation.

A single point mutation, also called a base substitution,
occurs when a single nucleotide is replaced with a different
nucleotide.

A point mutation results in a base pair substitution after

replication and possibly a mutant protein after transcription
and translation.

There are three types of point mutations:

Silent mutation
Missence Mutation
Nonsense Mutation

Silent Mutation

A silent mutation causes no change in the activity of the protein.

A silent mutation is usually the result of a substitution occurring

in the third location of the mRNA codon. Third base changes
often have no effect on the amino acid sequence of the protein.

The genetic code is degenerate (most amino acids are coded for
by several alternative codons), the resulting new codon may still
code for the same amino acid.

These mutations affect the DNA but not the protein. They have
no effect on the organisms phenotype.

Missence Mutation

A missence mutation is a nucleotide substitution that

changes a codon so that it codes for a different
amino acid in the protein.

Some missense mutations have very large effects,

while others have minimal or no effect. This usually
results in a change of the activity of the protein. The
change may be harmful or beneficial to the protein.
It depends on where the mutation occurs in the
proteins structure, and how big a change in the type
of amino acid it is.

Nonsense Mutation

A nonsense mutation is the same as a missense

mutation except the resulting codon codes for a
STOP signal.

The result is a premature termination of translation.

The protein is shorter than usual and does not

contain all the amino acids that it should. Therefore,
this protein is most likely nonfunctional.

Frameshift Mutations

Another type of mutation is a frameshift mutation

which is caused by the insertion or a deletion of a
base pair.

An inserted or deleted nucleotide alters the triplet

grouping of nucleotides into codons and shifts the
reading frame so that all nucleotides downstream
from the mutation will be improperly grouped.

The result is a protein with extensive missense

ending sooner or later in nonsense.

What causes mutations?

A mutation can be the result of different events.

Errors made during replication, repair, or

recombination can all lead to point or frameshift
mutations. Mutations resulting from such errors are
spontaneous mutations.

What causes mutations?

DNA replication is very accurate, but DNA polymerase is not

100% accurate. Mutations that are not due to external factors
are called spontaneous mutations.

Our body temperature (37oC) increases the rate of spontaneous

mutation. The base C spontaneously converts to the base U
readily at high temperatures.

A CG base pair can become a UG base pair. If the mismatch is

not detected and repaired before DNA replication begins, the U
will be paired with an A during replication. The UG will thus
become an UA and a CG base pair. Replacement of the U or
further replication will result in the UA becoming an TA base
pair. So, heat causes CG base pairs to become TA base pairs.

Environmental factors also influence

the rate of mutation

A mutation can also result from the action of

physical and chemical agents known as mutagens. We
will now explore three mutagens: nitrous acid, base
analogs, and UV light.

Nitrous Acid (HNO2)

Nitrous acid affects DNA complementation.

The acid randomly modifies the base adenine so that it will pair
with cytosine instead of thymine. HNO2 causes GC base pairs to
become AT base pairs, and AT base pairs to become GC base
pairs

This change is made evident during DNA replication when a new

base pair appears in daughter cells in a later generation.

The salt of nitrous acid (nitrite) can be found in preserved

meats and is mutagenic.

Nitrous acid (HNO2)

Base Analog

A base analog is a compound sufficiently similar to one of the

four DNA bases but have different pairing properties.

For example, 5-bromouracil is the analog of thymine but

sometimes pairs with guanine and 2-aminopurine is the analog of
adanine but sometimes pairs with cytosine. It can be
incorporated into DNA and pair with A or G. It results in AT to
GC changes or GC to AT changes

The incorporation of a base analog will to a base pair

substitution in that appears in daughter cells in a later
generation.

5-Bromouracil

X-rays & UV Light

Ionizing radiation (X-rays) & nuclear radiation cause

mutations by creating highly reactive free radicals
can cause minor or major mutations. They can react
with DNA and cause breaks in the DNA backbone.
This may destroy individual genes, or result in loss of
whole sets of genes through loss of pieces of
chromosomes.

UV rays from sunlight result in the formation of TT

dimers

UV Light

UV Light

Exposure to direct UV light induces covalent linking between

adjacent thymine nucleotides on a DNA strand forming a
thymine dimer.

These dimers cause the strand to buckle, disrupting normal base

pairing. This prevents proper replication and transcription.

Bacteria have enzymes to fix the damage created by UV light.

An enzyme cuts the DNA at two point and removes the damaged
portion.

UV Light

T-T dimers can be repaired, but if they remain unrepaired until

replication, the opposite strand will be replicated incorrectly.
DNA polymerase will skip the bases included in the dimer, and a
2 nucleotides will be lost from the DNA.

DNA polymerase synthesizes a new DNA segment using the

healthly strand as a template.

DNA ligase joins the new fragment to the old strand.

Mutation Rate

Mutations are random events and there is no way of

knowing when a mutation will occur.
Genes do, however mutate spontaneously at a
characteristic rate, making it possible to assign
probabilities to certain mutation events.
The probability that a gene will mutate when a cell
divides is called the mutation rate.

Mutation Rate

Spontanoeus mutation rate for the average gene is

0.000000001.
This means a mutation event is estimated to occur
once in every million genes replicated.

The presence of a mutagen increases the rate of

mutation to 0.00001 to 0.001.
This means that a mutation event is estimated to
occur once in every hundred thousand to one
hundred thousand genes in the presence of a
mutagen.

Alleles of a gene commonly

differ by only a single nucleotide
pair in DNA. The nucleotide
change results in an amino acid
change in the protein and a
change in the properties of the
protein.

Sickle-cell anemia

Sickle-cell anemia is due to a recessive gene.

Homozygotes for the sickle-cell allele have sicklecell anemia. They have problems delivering oxygen to
their tissues when they are stressed and oxygen
levels in their blood start to drop.

The gene codes for Hb, one of the two proteins

that make up the hemoglobin 2 molecule.

A single base-pair change in DNA can

account for the amino acid change
HbS, sickle cell hemoglobin, is a change in the betaglobin gene, where a GAG codon is converted to GUG.
GAG codes for glutamic acid, which is a hydrophilic
amino acid that carries a -1 charge, and GUG codes
for valine, a hydrophobic amino acid. This amino acid
is on the surface of the globin molecule, exposed to
water. Under low oxygen conditions,
valines affinity for hydrophobic
environments causes the
hemoglobin
to crystallize out of
solution.

-Hb has an amino acid sequence containing 146 amino acids.

In normal -Hb, the sixth amino acid is GLU
In sickle-cell -Hb, the sixth amino acid is VAL
in mRNA:
GLU is coded by either GAA or GAG
VAL is coded by GU_
Normal
Template:

... CTT ...

Sickle cell
anemia
... CAT ...

Coding:

... GAA ...

... GTA ...

Codon:

... GAA ...

... GUA ...

Amino
acid:

... GLUTAMIC
ACID ...

... VALIN ...

All genetic variation arises from change

in the
nucleotide sequences of DNA