Download MUTATION LEC

MUTATION
Mutations
Definition:
Mutations are changes made to the
nucleotide sequence of the
genetic material in a cell.
ERROR Textbook says
mutations are changes to the DNA
sequence that are inherited.
DON’T HAVE TO BE INHERITED
Are all Mutations Bad?
Nope.
Most mutations have no affect
whatsoever because they’re
either in non-coding regions,
not expressed or don’t affect
the structure of proteins.
Good Mutations
Some mutations improve
proteins making them better.
The passing on of improved DNA
is the basis of evolutionary
biology.
Mutation and CANCER
Cancer - disease where a group of
cells display uncontrolled division,
invasion and destruction of
adjacent tissues, and sometimes
metastasis (moving to new areas
via blood or lymph system)
Causes of CANCER
Cancer is caused when mutations
create oncogenes (cancer genes
that allow for really fast cell
growth and division) and
deactivate tumour suppressing
genes.
Its very rare for all these required
mutations to occur together and
cause cancer
Substitutions
The replacement of one base in
a DNA sequence by another
base. (Causes either silent
missense, or nonsense
mutations)
e.g.. ATCCAGGTCTC goes to
ATGCAGGGCTC
Substitutions can also be
referred to as
Point Mutations
Point Mutation are mutations at
a specific base pair in the
genome.
Silent Mutations
Substitutions that do not result in
a change in the amino acid
coded for by the codon.
Can also be point mutations, or
any type of mutation in a noncoding region
Silent Mutations
E.g.// Silent Point Mutation
TAC TTC GAG GCG
AUG AAG CUC CGC
Met Lys Leu Arg
TAC TTC GAT GCG
AUG AAG CUA CGC
Met Lys Leu Arg
No change because both CUC and
CUA code for Leucine
Missense Mutation
Substitution that results in a different
AA being coded for by a codon. Is
sometimes bad for cell. E.g. Sickle
Cell Anaemia
Nonsense Mutation
Substitution that causes a protein
coding codon to become a stop
codon
***often lethal to the cell
Frame shift Mutation
Any mutation that causes the
reading frame of codons to
change.
Can be caused by insertions,
deletions, translocations, and
transposable elements
INDELS
Insertions and Deletions
Insertions:
ATGCCAT  ATGAGGCCCAT
Deletions:
ATGGCACTGTGCA  ATGCA
Indels can involve the removal or addition of 1 or
thousands of bases
INDELS
Insertions: the placement of 1 or
more extra nucleotides into a
DNA sequence
Deletions: the removal of 1 or
more nucleotides from a DNA
sequence.
Translocations
The transfer of a fragment of
DNA from one site in the
genome to another.
E.g.:
ATCGCGCTTGCT 
ATTTGCGCGCCT
Translocations
Translocation can occur on much
larger scales:
Transposable Elements
Long segments of DNA that can
sometimes contains genes which
get “copied and pasted” or “cut and
pasted” (translocation) throughout
genome
Inversion
The reversal of a segment of
DNA within a chromosome.
E.g.:
ATGCTTGCATACAC
To
ATGTACGTTCACAC
Good Test Question: Which type of mutation can change
many bases and never causes a frameshift mutation?
--Inversions
Causes of Mutations
Spontaneous Mutations –
caused by accidental errors
made by genetic machinery of
the cell
Induced Mutations –
mutations caused by a
chemical agent, virus, or
radiation
RADIATION
Example of Direct Effect:
Tanning
UV rays from sunlight cause
mutations as well as a killer tan
Example: Tanning
UV rays create thymine dimers
Example: Tanning
Thousands of TT dimers are
formed each second in skin
cells while we tan. We repair
99.99% of these dimers, but
sometimes they cause bases
to change or move places.
X-Rays
X-rays are powerful
enough to break
bonds in the DNA
backbone. This
sometimes
causes mutation
Chemical Induced
Mutations
Chemicals react with DNA either
directly or indirectly which
sometimes causes base pairs
to change.
E.g.// 10% of the Oxygen we breath
doesn’t scoop up electrons from ETC,
but rips electrons off random
molecules in cells creating radicals
which can then react with DNA
potentially causing mutations
Ethanol
Increases risk of getting a
number of cancers.
E.g./ Bisphenol-A
Bisphenol-A may cause cancer if you boil
your beverage in a Nalgene for 120 hours
before drinking
Viruses
Some viruses activate
Oncogenes so the
cells they infect
work faster and
multiply to produce
new viruses faster
Virus Induced Mutation
E.g.// HPV – popular in media
due to Guardasil vaccine.
Causes cervical cancer. Also
causes throat cancer.
If you chew tobacco or smoke
you’re 3-4 times more likely to
get throat cancer. If you have
throat HPV you’re 32-56 times
more likely to get throat cancer.