1. Genetic Mutations
Good, bad or neutral?

2. Mutations Inheritable errors made in DNA during replication
3 broad groups:
Beneficial
Deleterious
Neutral
Most mutations are neutral, either because they occur in introns, or because of the redundancy inherent in our genome

3. 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

4. Causes of Mutations
1) Spontaneous mutations (copying errors) 2) Induced mutations (exposure to mutagens)

5. Spontaneous Mutations
Occur under normal conditions.
Caused by errors during DNA replication that are go uncorrected
May involve mispairing during replication
Can also be caused by errors made during crossover in meiosis

6. 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

7. Environmental Causes of Mutation

9. Physical Mutagens
For example, radiation

10. 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

12. Categories of Mutations
1. Point mutations
Mutations at a specific base pair on the genome
2. Chromosomal mutations
One DNA fragment is moved from one site on the genome to another

13. Types of DNA Replication Errors:
Small scale, point mutations effect only a small group of base pairs:
Substitution
Insertion or deletion
Inversion

14. 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?

15. 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.

16. Mutations: Substitutions
Substitution: TAG CAT GAG Becomes TCG CAT GAG = Similar protein with one different A.A

17. Mutations: Substitutions
Normal gene
GGTCTCCTCACGCCA ↓
CCAGAGGAGUGCGGU
Codons
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCACCTCACGCCA ↓
CCAGUGGAGUGCGGU
Pro-Arg-Glu-Cys-Gly
Substitutions will only affect a single codon
Their 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)

18. 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

19. No change Normal gene Substitution mutation GGTCTCCTCACGCCA↓
CCAGAGGAGUGCGGU
Codons
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTTCTCACGCCA ↓
CCAGAAGAGUGCGGU
Pro-Glu-Glu-Cys-Gly
© 2010 Paul Billiet ODWS

20. Disaster Normal gene Substitution mutation GGTCTCCTCACGCCA↓
CCAGAGGAGUGCGGU
Codons
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTCCTCACTCCA ↓
CCAGAAGAGUGAGGU
Pro-Glu-Glu-STOP
© 2010 Paul Billiet ODWS

21. Mutations: Insertions
Addition: TAG CAT GAG becomes TTA GCA TGA G

22. 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?

23. 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.

24. 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.

25. Mutations: Additions A frame shift mutation Normal gene
GGTCTCCTCACGCCA ↓
CCAGAGGAGUGCGGU
Codons
Pro-Glu-Glu-Cys-Gly
Amino acids
Addition mutation
GGTGCTCCTCACGCCA ↓
CCACGAGGAGUGCGGU
Pro-Arg-Gly-Val-Arg
© 2010 Paul Billiet ODWS

26. Mutations: Deletions
Deletion: TAG CAT GAG Becomes TGC ATG AG A

27. 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?

28. 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.

29. 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.

30. Mutations: Deletions A frame shift mutation Normal gene
GGTCTCCTCACGCCA ↓
CCAGAGGAGUGCGGU
Codons
Pro-Glu-Glu-Cys-Gly
Amino acids
Deletion mutation
GGTC/CCTCACGCCA ↓
CCAGGGAGUGCGGU
Pro-Gly-Ser-Ala-Val
© 2010 Paul Billiet ODWS

31. Inversion: AUG UUU UUG CCU UCC UUG UUU GUA
Two adjoining base pairs or entire chromosomal segment reverses its orientation.
Gene control is affected.

32. Inversion The reversal of a segment of DNA within a chromosome.
No gain or loss of genetic information.
A gene may be disrupted.

33. Translocation
Characterized by relocation of groups of base pairs from one place in the genome to another.
“Jumping genes” are called Transposable elements.

34. 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

35. 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.

36. 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?

37. 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:
Silent mutations
Missense mutations
Nonsense mutations
Frame shift mutations

38. Examples: Regular DNA Strand
Genetic code as inherited from parents:

39. 1) Silent Mutations
Due to the wobble effect, this base pair change has no effect on the amino acid produced

40. 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.

41. 2) Missense Mutations
Point mutation produces a different amino acid in the polypeptide chain
Can be neutral, harmful or beneficial

42. Substitutions: Missense Mutation
A single substitution of one base in a codon, resulting in a different amino acid.
E.g., Sickle cell anemia.

43. Sickle Cell Anaemia Sickle cell anemia Blood smear (normal)
Image Credit:
Blood smear (normal)
Image Credit:

44. 3) Nonsense Mutations
Point mutation produces a premature STOP codon rather an amino acid
Protein produced is usually non-functional

45. 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

46. 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.

47. Question:
Why would the deletion of 3 nucleotides be better then 2?

48. Review of Mutation Effects: