Alteration of Cellular

Information
Introduction to Biotechnology
MUTATION
• Error during DNA replication that results in a change in the sequence of
deoxyribonucleotide bases
• Two types of Mutations:
– Spontaneous
– Induced
Spontaneous Mutation
• Substitution of a nucleotide (point mutations)
• Point mutations have a variety of effects on the downstream protein
product—consequences that are moderately predictable based upon
the specifics of the mutation
Spontaneous Mutation
• Deletion or addition of a nucleotide
Results of Spontaneous Mutation
• Missense mutation This is usually seen with a single substitution
mutation and results in one wrong codon and one wrong amino acid.
• Missense mutations can render the resulting protein
nonfunctional,and such mutations are responsible for human diseases
such as Epidermolysis bullosa, sickle-cell disease, and SOD1 mediated
ALS.
Results of Spontaneous Mutation
• Nonsense mutation - If the change in the deoxyribonucleotide base
sequence results in transcription of a stop or nonsense codon, the
protein would be terminated at that point in the message.
• Some genetic disorders, such as thalassemia and DMD, result from
point-nonsense mutations.
Results of Spontaneous Mutation
• Sense mutation - This is sometimes seen with a single substitution
mutation when the change in the DNA base sequence results in a new
codon still coding for the same amino acid.
Results of Spontaneous Mutation
• Frameshift Mutation - This is seen when a number of DNA
nucleotides not divisible by three is added or deleted.
Induced Mutation
• Caused by mutagens, substances that cause a much higher rate of
mutation.
– Ultraviolet radiation
– X-rays and gamma rays
– Chemicals
• Caused by usage of Recombinant DNA technologies
• CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)
Mutation as a result of Ultraviolet rays
CRISPR
• The CRISPR/Cas system is a
prokaryotic immune system
that confers resistance to
foreign genetic elements such
as those present within
plasmids and phages that
provides a form of acquired
immunity. RNA harboring the
spacer sequence helps Cas
(CRISPR-associated) proteins
recognize and cut exogenous
DNA. Other RNA-guided Cas
proteins cut foreign RNA.
Chemical Mutagens
• An overview of some of the
major chemical mutagens and
their modes of action is given in
the following table. Several
classes of chemical mutagens
exist. The nucleotide base
analogs are molecules that
resemble the purine and
pyrimidine bases of DNA in
structure yet display faulty
pairing properties.
Mutations That Arise from DNA Repair
• Lesions on the template DNA may lead to stalling of DNA replication,
which is a lethal event. Stalled replication, as well as certain types of
major DNA damage, activate the SOS repair system.
• The SOS system initiates a number of DNA repair processes, some of
which are error-free. However, the SOS system also allows DNA repair
to occur without a template, that is, without base pairing; as expected,
this results in many errors and hence many mutations. This permits cell
survival under conditions that are otherwise lethal.
DNA Repair Systems