Base Mutations on Protein
Function and Phenotypes
First Recall Proteins-----
Polypeptides made up of amino acids

Proteins are polypeptides, numerous amino acids
**Peptide
Bond between
amino acids
**Notice the “R”
group. It’s a group
of molecules that
determines the
amino acid.


The amino acid sequence determines the protein!!
Shape-specific

Example - The sequence for a specific enzyme will be totally different
from that of a hormone!
Human Growth Hormone
Amylase Enzyme
Amino Acid Sequence - Polypeptide
Basic Types of Proteins
Structural Proteins


Forms part of cell materials
Provides support


fibrous and stringy and provide support.
Examples: Keratins strengthen protective
coverings such as hair, quills, feathers, horns,
and beaks. include keratin
Collagen, and elastin are examples. Collagens
and elastin provide support for connective tissue
such as tendons and ligaments.
Functional Proteins

Hormones – Chemical Signals released by a cell or a gland in one part
of the body that sends out messages that affect cells in other parts of
the organism






Growth and development
Metabolism - how your body gets energy from the foods you eat
Sexual function
Reproduction
Mood
Enzymes – catalyze chemical reactions.


Example – Amylase is the enzyme that breaks starches in your
mouth. Speeds up the rate of digestion.
Nearly all biochemical reactions require them!
** Newly synthesized DNA is EXACTLY the same as the parent
DNA……or is it??
Mistakes Can Occur!!


Remember that DNA is replicated during the S phase
of Interphase of the cell cycle and during Meiosis (the
formation of gametes)
Mutations may or may not change the function of a
protein

May change phenotype or how a gene is expressed

Example: brown hair is a phenotype, sickle cell anemia is
a phenotype, dwarfism is a phenotype
Mutations
***Errors usually occur during DNA replication and
transcription by external agents called mutagens
(chemicals, radiation, X-rays etc.)
***Some occur randomly and some phenotypes
are selected for in nature
***Although mutations can cause problems, if it
weren’t for mutations, we wouldn’t have new genes
such as those for green eyes
“Fixing” Errors



Enzymes proofread as bases are paired during
replication and replace those wrongly paired
Other enzymes police the replication process
But…………
Mutations Change a DNA Sequence
and May Affect a Gene

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May be random or spontaneous.
When genes have an error in their DNA code, they
may not work properly, and are said to be "altered"
or mutated.
DNA damage from environmental agents such as
radiation (sunlight), nuclear radiation, some viruses,
some chemicals, genetics, inflammation, infection



Mistakes that occur when a cell copies its DNA in
preparation for cell division.
Can occur during meiosis (making of sperm, and egg)
Changes mRNA codons
Mismatched Base Pair Can
Occur – Usually Random
Spontaneous Mutations Environmental agents such as
nuclear radiation can damage DNA by breaking bonds
between nucleotides on either side of the DNA molecule
can occur
Mutated Cells


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Some mutated cells will be defeated by the body's immune
system
others may undergo apoptosis, or “cell suicide”.
occasionally a cell with mutations slips through proofreading
safeguards.
When mutations accumulate, the genetic material is so scrambled
that the cell no longer acts like a normal, healthy cell.
Tumors, mass of cells that have no purpose, may form
Benign Tumors (non-cancerous)




Not malignant tumor (cancerous)
Does not invade nearby tissue or spread to other parts of the
body the way cancer can.
But benign tumors can be serious if they press on vital structures
such as blood vessels or nerves.
Some, such as colon polyps, can become cancerous
Cancerous Tumor (malignant)


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Abnormal cells grow uncontrolled
Invades surrounding tissues
Usually capable of producing metastases
(spread to other organs)
May recur after attempted removal
May cause death of the host unless adequately
treated
Mutations and Reproduction
**Mutations can occur during meiosis, the
making of sperm or egg and can be passed
along to offspring
**Example: Achonroplasia is a type of
dwarfism that can come from a
mutation during sperm formation
**The mutation may produce a new trait
(good OR bad)
.
Types of Base Mutations
** Point mutations, base substitution, affects a single base
**Frameshift – Addition or deletion of a base – Affects entire
protein
Base Pair Substitution –
AKA Point Mutation
Point Mutations


Affects a single base and change the codon
May or may not affect the amino acid

Sometimes if the third base of the codon changes,
the amino acid may stay the same!

UCU
UCC
UCA
UCG



ALL code for Ser
Base Substition MAY or MAY NOT Change the Protein
TACCAGGATTAACATGGAAGTGTAATC
DNA
AUGGUCCUAAUUGUACCUUCACAUUAG
mRNA
Met
Val
Leu
Ile
Val
Pro
Ser
His (STOP)
What if the C was substituted with an A ?????
TACCAGGATTAA AATGGAAGTGTAATC
AUGGUCCUAAUUUUACCUUCACAUUAG
Met
Val
Leu
Ile
Leu
Pro
Ser
DNA
mRNA
His (STOP)
REMEMBER if the 4rd base is changed, it may not change the protein!
Base Substitution Example
Sickle Cell Anemia – red blood cells have a protein on their surgface
called hemoglobin that carry oxygen. Patients with this affliction have
misshaped (sickle-shaped) red blood cells and cannot carry enough
oxygen
**Notice the DNA sequence below.. A is substituted for a T
Frameshift Mutation

Insertion (addition) or deletion of a base shift the frame of bases
left or right, changing the amino acids affecting the whole
protein. It won’t function properly
Frame-Shift Addition
Example: Addition of a T beside of the C... shifts the
entire protein over to the right– changes ENTIRE
PROTEIN – There is NO STOP CODON!!
TACCAGGATTAACATGGAAGTGTAATC
AUGGUCCUAAUUGUACCUUCACAUUAG
Met
Val
Leu
Ile
Val
Pro
Ser
DNA
mRNA
His (STOP)
TACCAGGATTAA CTATGGAAGTGTAATC… DNA
AUG GUC CUA AUUGAUACCUUCACAUUAG…mRNA
Met
Val
Leu
Ile
Asp
Thr
Phe
Thr Leu
Extra Base
Frameshift Deletion
Example: Deletion of the C... shifts the entire protein
over to the Left– changes ENTIRE PROTEIN – There
is NO STOP CODON!!
TACCAGGATTAACATGGAAGTGTAATC
AUGGUCCUAAUUGUACCUUCACAUUAG
Met
Val
Leu
Ile
Val
Pro
Ser
DNA
mRNA
His (STOP)
TACCAGGATTAA ATGGAAGTGTAATC…
AUG GUC CUA AUU UACCUUCACAUUAG…
Met
Val
Leu
Ile
Thr
Leu His
Ile
Ser or Arg
DNA
mRNA