Base Mutations on Protein Function and

Phenotypes

Polypeptides made up of amino acids Proteins are polypeptides, numerous amino

acids

First Recall Proteins------

**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!

Amino Acid Sequence - Polypeptide

Human Growth HormoneAmylase Enzyme

Basic Types of 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.

Structural 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!

Functional Proteins

** Newly synthesized DNA is EXACTLY the same as the parent DNA……or is it??

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

Mistakes Can Occur!!

***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

Mutations

Enzymes proofread as bases are paired during replication and replace those wrongly paired

Other enzymes police the replication process

But…………

“Fixing” Errors

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

Mutations Change a DNA Sequence and May Affect a

Gene

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

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

Mutated Cells

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

Benign Tumors (non-cancerous)

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

Cancerous Tumor (malignant)

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

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

Point Mutations

ALL code for Ser

TACCAGGATTAACATGGAAGTGTAATCAUGGUCCUAAUUGUACCUUCACAUUAG

Met Val (STOP)HisSerProVal IleLeu

DNA

mRNA

Base Substitution MAY or MAY NOT Change the Protein

Met Val IleLeu

TACCAGGATTAAAUGGUCCUAAUU

AATGGAAGTGTAATC DNA

UUACCUUCACAUUAG mRNA

Leu (STOP)HisSerPro

What if the C was substituted with an A ?????

REMEMBER if the 3rd base is changed, it may not change the protein!

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

Base Substitution Example

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

Frameshift Mutation

Met Val IleLeu

TACCAGGATTAAAUG GUC CUA AUU

CTATGGAAGTGTAATC… GAUACCUUCACAUUAG…

Asp Phe ThrThr

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!!

Leu Extra Base

Frame-Shift Addition

TACCAGGATTAACATGGAAGTGTAATC

AUGGUCCUAAUUGUACCUUCACAUUAG

(STOP)HisSerProValMet Val IleLeu

DNA

mRNA

DNA

mRNA

Met Val IleLeu

TACCAGGATTAAAUG GUC CUA AUU

ATGGAAGTGTAATC… UACCUUCACAUUAG…

Thr His IleLeu Ser or Arg

Frameshift Deletion

TACCAGGATTAACATGGAAGTGTAATC

AUGGUCCUAAUUGUACCUUCACAUUAG

(STOP)HisSerProValMet Val IleLeu

DNA

mRNA

DNA

mRNA

Example: Deletion of the C... shifts the entire protein over to the Left– changes ENTIRE PROTEIN – There

is NO STOP CODON!!