Mutations

Spiderman bite

Mutation

• A mutation is a change in an organism resulting from a chemical change in the structure of a gene.

• A mutation occurs because of the alteration in one or more base pairs of the DNA molecule.– substitution of one base pair for another. (point mutation)– abnormal base pairing. (point mutation)– extra base is added/deleted (frame shift mutation)

Types of MutationsGerminal Mutations: Occur in the DNA of the germ or sex cells

– Can be passed on to offspring, ie. Effect the next generation. Ex. Hemophilia

Somatic Mutations: Occur in the body cell.-Not inheritable by next generation.-Affects the individual who gets it. Ex. Cancer

Mutagen• Any agent that causes mutations in humansChemical Radiation Biological

Change will first be reflected in the RNA copy, then in the protein that the RNA codes for, and finally in the appearance of new traits in the living organism.

Chemical Radiation BiologicalAromatic amines X-rays Viruses/retrovirusCyanide Gamma raysArsenic UV lightCarbon monoxideformaldehydeAsbestosCigarette smoke

Gene Mutation• Affect only a single geneCaused by: Deletion: one base is left out changes all the codons following it Addition: one base is added changes all the codons following it Substitution: pieces are replaced with each other only ONE codon is affected

• Mutations where bases are added or deleted are called frameshift mutations

• The effect on the individual depends on the gene's role.

Example

EXAMPLE OF THE EFFECT OF A GENE MUTATION:

ORIGINAL MESSAGE: THE BIG DOG BIT TED AND RAN OFF

DELETION/FRAMESHIFT:

THE BID OGB ITT EDA NDR ANO FF

Try it for yourself: Here is a section of DNA before a mutation

DNA T A C G G G C T C T A G C G A G A T A T TmRNA

a.a.

DNA T A C G G G C T C T A G C G A G A T A T TmRNA A U G C C C G A G A U C G C U C U A U A Aa.a. Methionine Proline Glut. acid Isoleucine Alanine Leucine Stop

Here the same section is after one extra base (a G in the third codon) has been added to the original sequence.

DNA

T A C G G G G C T C T A G C G A G A T A T mRNA

a.a.

DNA

T A C G G G G C T C T A G C G A G A T A T mRNA A U G C C C C G A G A U C G C U C U A U A a.a. Methionine Proline Arginine Asp. Acid Arginine Serine Isoleucine

What effect does addition or deletion of bases have?

• Amino acid sequence is changed, so the overall protein is different

• New protein may have new or no function

Substitution/Point mutations

• One nucleotide is incorrectly substituted for another

ORIGINAL MESSAGE: THE BIG DOG BIT TED AND RAN OFF

SUBSITUTION OF D TO S:

THE BIG DOG BIT TES AND RAN OFF

Here the same section is after one base (a C in the third codon) has been substituted to the original sequence.

DNA

T A C CG G C T C T A G C G A G A T A T T mRNA a.a.

DNA T A C CG G C T C T A G C G A G A T A T T mRNA A U G GC C G A G A U C G C U C U A U A Aa.a. Methionine Alanine Glut. acid Isoleucine Alanine Leucine Stop

DNA T A C G G G C T C T A G C G A G A T A T TmRNA A U G C C C G A G A U C G C U C U A U A Aa.a. Methionine Proline Glut. acid Isoleucine Alanine Leucine Stop

Original Sequence

Mutated Sequence

What effect does this substitution have?

The subsitiution changed 1 aa. Protein is different, function changed or lost.

Another substitutionDNA T A C G G G C T C T A G C G A G A T A T TmRNA A U G C C C G A G A U C G C U C U A U A Aa.a. Methionine Proline Glut. acid Isoleucine Alanine Leucine Stop

Original AA sequence

DNA T A C G G C C T C T A G C G A G A T A T TmRNA

a.a.

DNA T A C G G C C T C T A G C G A G A T A T TmRNA A U G C C G G A G A U C G C U C U A U A Aa.a. Methionine Proline Glut. acid Isoleucine Alanine Leucine Stop

Substitution of the last G on the 2nd codon

What effect does this substitution have?

None, the protein has the same aa sequence, therefore shape and function will remain the same

How do you explain why mutations due to DNA replication are so rare?

• DNA polymerase proof reads and corrects any changes to DNA

The good, bad and the ugly

• Usually random changes are HARMFUL (frequently mutations are lethal).

NEGATIVE MUTATION• BENEFICIAL MUTATION- About one time in

million, the change might actually improve the protein POSITIVE MUTATION

• Some mutations have no effectSILENT MUTATION

Most birth defects result from a chromosomal abnormality. The abnormality most frequently appears during meiosis when the egg and sperm cells are formed.

Gene mutations

• Ex. Sickle Cell Anemia• Normal round-shaped red

blood cells are intermingled with some having a sickle shape.

• This disease occurs when one amino acids present in hemoglobin is misplaced because of an error in the messenger RNA which was made by a piece of DNA with one of its base pairs out of arrangement.

Albinism

• If the enzyme that converts tyrosine to melanin is defective, albinism occurs. These subjects will have no skin or hair pigment, and hence appear almost pure white.

Down’s Syndrome (trisomy 21)

• Such children are born with an extra chromosome #21 (47 chromosomes instead of the normal 46).

• During the formation of the egg, both number 21 chromosomes end up in the same egg cell.