genetic mutations good, bad or neutral?. mutations inheritable errors made in dna during replication...

Genetic Mutations

Good, bad or neutral?

Mutations

Inheritable errors made in DNA during replication

3 broad groups:BeneficialDeleteriousNeutral

Most mutations are neutral, either because they occur in introns, or because of the redundancy inherent in our genome

Mutations Mistakes in the DNA sequence can alter

the function of proteins produced Diploid organisms have two copies of each

gene so error may be masked in the phenotype

Causes of Mutations1) Spontaneous mutations (copying errors)

2) Induced mutations (exposure to mutagens)

Spontaneous Mutations

Occur under normal conditions. Caused by errors during DNA replication that

are go uncorrected May involve mispairing during replicationCan also be caused by errors made during

crossover in meiosis

Induced Mutations: 2 kinds of mutagens:

Physical mutagens physically damage DNA strands (X-rays, UV light)

Chemical mutagens alter the molecular structure of DNA without damaging it physically (carbon monoxide, ethidium bromide)

Note: mutagens that also cause cancer are called carcinogens

Environmental Causes of Mutation

Physical Mutagens

For example, radiation

Causes of Genetic Mutations

Cancer is a genetic disease because it is always a result of a mutation in the genetic sequence.

Mutations result in oncogenes - genes that control cell growth and division.

Cancer

Categories of Mutations

1. Point mutationsMutations at a specific base pair on the

genome

2. Chromosomal mutationsOne DNA fragment is moved from one site on

the genome to another

Types of DNA Replication Errors:Small scale, point mutations effect only a small group of base pairs:SubstitutionInsertion or deletionInversionhttp://www.youtube.com/watch?v=kp0esidDr-c

Analogy:

Split this sentence into codons!

Thesunwashotbuttheoldmandidnotgethishat.It should look like this...

The sun was hot but the old man did not get his hat.What if we substituted one of the letters?

Substitution Analogy:

The sun was hot but the old man did not get his hat.

The son was hot but the old man did not get his hat.

The bun was hot but the old man did not get his hat.

Mutations: Substitutions

Substitution:

TAG CAT GAG

Becomes

TCG CAT GAG

= Similar protein with one different A.A

Mutations: SubstitutionsSubstitution mutation

GGTCACCTCACGCCA

↓

CCAGUGGAGUGCGGU

↓

Pro-Arg-Glu-Cys-Gly

Substitutions will only affect a single codonTheir effects may not be serious unless they affect an amino acid that is essential for the structure and function of the finished protein molecule (e.g. sickle cell anaemia)

Normal gene

GGTCTCCTCACGCCA

↓

CCAGAGGAGUGCGGU

Codons

↓

Pro-Glu-Glu-Cys-Gly

Amino acids

The genetic code is degenerate

A mutation to have no effect on the phenotype

Changes in the third base of a codon often have no effect.

(The wobble hypothesis)

© 2010 Paul Billiet ODWS

No changeNormal gene

GGTCTCCTCACGCCA

↓

CCAGAGGAGUGCGGU

Codons

↓

Pro-Glu-Glu-Cys-Gly

Amino acids

Substitution mutation

GGTCTTCTCACGCCA

↓

CCAGAAGAGUGCGGU

↓

Pro-Glu-Glu-Cys-Gly

© 2010 Paul Billiet ODWS

DisasterNormal gene

GGTCTCCTCACGCCA

↓

CCAGAGGAGUGCGGU

Codons

↓

Pro-Glu-Glu-Cys-Gly

Amino acids

Substitution mutation

GGTCTCCTCACTCCA

↓

CCAGAAGAGUGAGGU

↓

Pro-Glu-Glu-STOP

© 2010 Paul Billiet ODWS

Addition:

TAG CAT GAG

becomes

TTA GCA TGA G

Mutations: Insertions

Analogy:

Split this into codons!

Thesunwashotbuttheoldmandidnotgethishat. It should look like this...

The sun was hot but the old man did not get his hat.

What if we added an extra letter?

Analogy: Insertion

Split this sentence into codons:

Thesunwashotbuttheoldmandidnotgethishatt.

Does this sentence still make sense?The sun was hot but the old man did not get his hat t.

Analogy: Insertion

Split this sentence into codons:

Theesunwashotbuttheoldmandidnotgethishat.

Does this sentence still make sense?

The esu nwa sho tbu tth eol dma ndi dno tge thi sha t.

Mutations: Additions

Normal gene

GGTCTCCTCACGCCA

↓

CCAGAGGAGUGCGGU

Codons

↓

Pro-Glu-Glu-Cys-Gly

Amino acids

Addition mutation

GGTGCTCCTCACGCCA

↓

CCACGAGGAGUGCGGU

↓

Pro-Arg-Gly-Val-Arg

A frame shift mutation

© 2010 Paul Billiet ODWS

Mutations: Deletions

Deletion:

TAG CAT GAG

Becomes

TGC ATG AG

A

Analogy:

Split this into codons!

Thesunwashotbuttheoldmandidnotgethishat. It should look like this...

The sun was hot but the old man did not get his hat.

What if we removed a random letter?

Analogy: Insertion

Split this sentence into codons:

Thesunwashotbuttheoldmandidnotgethisht.

Does this sentence still make sense?The sun was hot but the old man did not get his ht.

Analogy: Insertion

Split this sentence into codons:

Heesunwashotbuttheoldmandidnotgethishat.

Does this sentence still make sense?

Hes unw ash otb utt heo ldm and idn otg eth ish at.

Mutations: Deletions

Normal gene

GGTCTCCTCACGCCA

↓

CCAGAGGAGUGCGGU

Codons

↓

Pro-Glu-Glu-Cys-Gly

Amino acids

Deletion mutation

GGTC/CCTCACGCCA

↓

CCAGGGAGUGCGGU

↓

Pro-Gly-Ser-Ala-Val

A frame shift mutation

© 2010 Paul Billiet ODWS

Inversion: Two adjoining base

pairs or entire chromosomal segment reverses its orientation.

Gene control is affected.

AUG UUU UUG CCU

UCC UUG UUU GUA

Inversion The reversal of a segment of DNA within a

chromosome. No gain or loss

of genetic information. A gene may be

disrupted.

Translocation Characterized by relocation of groups of

base pairs from one place in the genome to another.

“Jumping genes” are called Transposable elements.

Translocation The transfer of a

fragment of DNA from one site in the genome to another location.

Usually occurs between two nonhomologous chromosomes.

Result is a fusion protein with an altered function

Transposable Elements Also known as “jumping genes”. Certain fragments of DNA

consistently move from one location to another.

If they are added to a coding region of a gene, it will leave it inactive.

Effects of DNA Mutations

Single point mutations in the population cause genetic variations in individuals called SNPs (single nucleotide polymorphisms)

They are very common and variable in non-coding portions of the genome

Why?

Effects of DNA Mutations

As you can see, the type of error can have very different effects on protein production.

Mutations can be categorized into 4 groups:

1.Silent mutations

2.Missense mutations

3.Nonsense mutations

4.Frame shift mutations

Examples: Regular DNA Strand

Genetic code as inherited from parents:

1) Silent Mutations Due to the wobble effect, this base pair

change has no effect on the amino acid produced

Silent Mutation Does not result in a phenotypic

change. Primarily occurs in the introns. Could be due to redundancy of

genetic code e.g. phenylalanine coded for by UUU and UUC…a change in the 3rd base does not change the amino acid.

2) Missense Mutations Point mutation produces a different amino

acid in the polypeptide chain Can be neutral, harmful or beneficial

Substitutions: Missense Mutation

A single substitution of one base in a codon, resulting in a different amino acid.

E.g., Sickle cell anemia.

Sickle Cell Anaemia

Blood smear (normal)Image Credit: http://lifesci.rutgers.edu/~babiarz/

Sickle cell anemiaImage Credit: http://explore.ecb.org/

3) Nonsense Mutations Point mutation produces a premature

STOP codon rather an amino acid Protein produced is usually non-functional

4) Frameshift Mutations Insertion or deletion shifts the entire reading

frame of the codons, usually resulting in different amino acids being incorporated from that point onwards.

Eg. Tay sachs

Frameshift Mutation Causes changes in the reading frame. Caused by an insertion:

Addition of one or more base pairs in a DNA sequence.

Caused by a deletion: Removal of one or more base pairs in a DNA

sequence.

Question:

Why would the deletion of 3 nucleotides be better then 2?

Review of Mutation Effects:

Mutations

SubstitutionsFrame shift Mutations

Cross over Mutations

Missense Mutations

Nonsense Mutations

Deletion Insertion Inversion TranslocationSegment Deletion/

Segment Duplication