1. Mutations

2. General types of Mutations
A mutation is a change in the normal DNA sequence.
They are usually neutral, having no effect on the fitness of the organism.

3. Introduction
Or they are harmful, and are responsible for many disorders.

4. General types of Mutations
Sometimes, beneficial mutations occur, which cause the “mutants” to better survive in their environment.
These mutations lead to adaptations and are the basis for the theory of Evolution by Natural Selection.

5. There are 2 General Categories of Mutations
Single gene Mutations
Changes in nucleotide sequence of one-gene
Chromosomal Mutations
Changes in chromosomes, involve many genes

6. Types of Single Gene Mutations

7. A) Point mutations a change in one nucleotide OR base pair in a gene
Often involves a substitution mutation where one base pair is switched for another.
Can also be a single base pair insertion or deletion.

8. Substitutions, Insertions and Deletions
Usually occur due to an uncorrected mistake in DNA replication.
Insertions can be fixed by exonucleases.
Deletions are rarely reversible.

9. The effects of Point mutations on Protein
A point mutation is not a problem if it occurs in an intron section of DNA.
A point mutation may cause problems if it occurs in an exon region of DNA , since these areas of DNA code for protein.

10. Frameshift Mutation
Insertion and Deletion mutations (but NOT substitution mutations) can result in frameshift mutations.
If a number of nucleotides is added or removed that is not a factor of 3 this causes the entire reading frame of the gene to be altered.

11. Frameshift Mutations Analogy: THE CAT ATE THE RAT - delete C
THE ATA TET HER AT no longer makes sense
THE CAT ATE THE RAT - add BAD
THE BAD CAT ATE THE RAT still makes sense

12. Frameshift Mutations

13. The effects of mutations on Protein
There are 3 main categories for how mutations affect the amino acid sequence of the protein:

14. 1) Silent Mutations
Due to the redundant nature of the genetic code the mutation codes for the same amino acid

15. 2) Missense mutations
the mutation codes for a different amino acid

16. Missense Mutation Examples
Can be harmful, for example alkaptonuria- most often due to a substitution mutation leading to a missense mutation.
Alters the gene for the enzyme that degrades tyrosine ;
Due to the faulty enzyme, homogentisic acid accumulates in the body, causes black urine damages cartilage &heart valves, causes kidney stones

17. Missense Mutation Examples
Sickle Cell Anemia is another disease caused by a single base pair substitution leading to a missense mutation.

18. Missense Mutation Examples
Missense Mutations can also be beneficial and may play a role in creating new proteins, such as antibodies, for fighting new infections.

19. 3) Nonsense Mutations
the change results in a premature stop codon.

20. Nonsense Mutations
Can be lethal to the cell, usually very harmful to the organism.

21. Chromosomal Mutations
Change to the chromosome number is always detrimental, if not lethal, to the organism

22. Chromosomal Mutations
Mutations can also involve rearrangement of genetic material which may affect several genes and several chromosomes and therefore protein synthesis.

23. Chromosomal Deletions and Duplications
Deletions result in a loss of genes
Duplications result in multiple copies of genes or even chromosomes.

24. Inversions
An inversion is the reversal of a segment of DNA in a chromosome.

25. Translocations
A translocation is the trading of chromosomal segments between two different chromosomes.

26. Translocations
They are usually not the same size segment being traded.
Some forms of cancer are caused by translocations (i.e. leukemia).

27. CAUSES OF MUTATIONS Spontaneous mutations occur naturally
Induced mutations are caused by environmental factors.
Causes of Spontaneous mutations include:
Errors in DNA replication
DNA transposition

28. DNA Transposition
movement of specific DNA sequences, called transposable elements, or transposons, within and between chromosomes.
Described by Barbara McClintock (American geneticist) 1949.

29. Causes of Induced mutations
A mutagen or mutagenic agent is a substance or event that increases the rate of mutation.

30. Physical Mutagens cause physical damage to DNA
X-Rays – point mutations and chromosomal deletions
UV radiation – causes reactions between adjacent pyrimidine bases (C and T)

31. Chemical Mutagens
Chemical mutagens react chemically with DNA to cause a nucleotide substitution or frameshift mutation.
May also have a similar structure to a nucleotide but with different base pairing properties

32. Examples of Chemical Mutagens
Nitrites (small amounts in cured meats)
Gasoline fumes
50+ compounds found in cigarette smoke
Most chemical mutagens are also carcinogenic

33. DNA Repair
Mutations that accumulate too rapidly or are very harmful do not provide a selective advantage.
The DNA polymerase enzymes can repair errors made in DNA replication.

34. DNA Repair
Mismatch repair by Mut proteins also helps to reduced replication errors.
Cells have other mechanisms that recognize and repair DNA that becomes damaged.

35. Examples of DNA Repair
Photorepair is used to correct UV radiation damage. A photolyase enzyme uses visible light to cleave the bond made between adjacent pyrimidines.
Excision repair enzymes recognize and remove many different forms of damage, a DNA polymerase enzymes rebuild the removed segment.

36. Conclusion
Mutations are usually _______________and have no effect on the organism.
However, when mutations are _____________, they can have lethal effects.
_____________ mutations are rare and result in ____________________.

37. Conclusion _______________________affect one nucleotide
_______________________are caused by insertions or deletions of nucleotides.
The result of a mutation on the protein is considered __________ (no effect), _____________ (single amino acid change) or ______________ (premature stop codon).

38. Conclusion
Chromosomes can have _______________, ___________________, _______________, and ___________________… all of which affect protein production and can lead to genetic disorders.
Stay away from _____________________as much as possible if you want to minimize your chances of accumulating mutations.