1. Changes in DNA that affect genetic information
MUTATIONS
Changes in DNA that affect genetic information

2. Mutation change in the genetic material of a cell Germ Cell Mutations
Somatic
Mutations
occur in sex cells and
are passed
on to
offspring
take
place in
body cells

3. Types of Mutations
Gene mutations result from changes in a single gene.
Chromosomal Mutations involve changes at chromosome level.
Point Mutations – Changes in one or a few nucleotides

4. Point Mutation: Base Substitution
DNA
mRNA
Amino Acids T A A U
methionine
isoleucine G C G C G C A T C G U A
arginine
threonine

5. 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.

6. Substitution: No change
Normal gene
GGTCTCCTCACGCCA ↓
CCAGAGGAGUGCGGU
Codons
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTTCTCACGCCA ↓
CCAGAAGAGUGCGGU
Pro-Glu-Glu-Cys-Gly
A mutation may have no effect on the phenotype.
Changes in the third base of a codon often have no effect. Example: CTC and CTT both code for Glutamine (Glu).

7. Substitutions: Disaster
Normal gene
GGTCTCCTCACGCCA ↓
CCAGAGGAGUGCGGU
Codons
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTCCTCACTCCA ↓
CCAGAAGAGUGAGGU
Pro-Glu-Glu-STOP

8. Point Mutation: Frameshift Mutation
Inserting or deleting a nucleotide causes the entire code to “shift.”
Insertion
THE FAT CAT ATE THE RAT
THE FAT CAT XAT ETH ERA T
Deletion
THE FAT CAT ATE THR AT

9. Example of Frameshift Mutation
DNA
mRNA
Amino Acids T A A U
methionine
isoleucine T C G A T A G C U A
alanine
arginine
threonine
tyrosine
Example of Frameshift Mutation

10. Mutations: Insertions
Addition of a nucleotide causes 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

11. 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

12. Gene Mutations
Frameshift Mutations – Shifts the reading frame of the genetic message
so that the protein may not be able to perform its function.
INSERTION
THE FAT CAT ATE THE RAT
THE FAT HCA TAT ETH ERA T
DELETION
TEF ATC ATA TET GER AT H H

13. Chromosomal Mutations
Deletion: Part of a chromosome is deleted
Duplication: Part of a chromosome is duplicated
Inversion: Chromosome twists and inverts the code.
Translocation: Genetic information is traded between non-homologous chromosomes.

15. Types of Chromosome Mutations
1. Deletion
occurs
when a piece
of a
chromosome
breaks off X X

16. 2. Duplication
Occurs when a gene sequence is repeated.

17. 2. Inversion
occurs when a piece breaks from a chromosome and reattaches itself to the chromosome in the reverse orientation

19. Deletion in Chromosome 16

20. 3. Translocation
Switch
occurs when a broken piece of a chromosome attaches to a non homologous chromosome

21. Philadelphia Chromosome

22. Philadelphia Chromosome

23. What Causes Mutations? DNA can become mutated
1. Mutations can be inherited
Parent to child
2. Mutations can be acquired
Environmental agents (mutagens)
Pesticides
Tobacco
UV radiation
Nuclear radiation
Mistakes when DNA is copied

24. Significance of Mutations
Most are neutral
Eye color
Birth marks
Some are harmful
i.e. Down Syndrome
Some are beneficial
Sickle Cell Anemia to Malaria
Immunity to HIV
Evolution - Genetic variability

25. Objectives:
Describe gene regulation in prokaryotes.
Explain how most eukaryotic genes are regulated.
Relate gene regulation to development in multicellular organisms.

26. Prokaryotic Gene Regulation
Prokaryotes regulate their activities using only those genes necessary for the cell to function.
OPERON: Group of structural and regulating genes that function as a single unit.

27. Prokaryotic Gene Regulation
Operons are composed of 4 components:
Regulator gene: Codes for a DNA binding protein known as a repressor (prevents RNA polymerase from binding to DNA.
Promoter: Region of DNA where RNA polymerase attaches to signal the start of transcription.
Operator: Turns transcription on or off by either allowing RNA polymerase to attach to the promoter or not.
Structural genes: Group of 3 genes that code for enzyme or proteins.

28. The Lac Operon
When E. Coli (bacteria) is denied glucose and given the milk sugar lactose instead, it immediately begins to make the 3 enzymes needed to metabolize lactose.
The 3 structural genes that code for these enzymes are next to each other on the DNA strand and are under the control of a single promoter and a single operator.

29. The Lac Operon – Lactose Absent
When lactose is absent, the regulator gene codes for a repressor that binds to the operator.
This prevents RNA polymerase from binding to the promoter.
Transcription for the enzymes needed to digest lactose does not take place. (It is unnecessary to waste the energy)

30. The Lac Operon – Lactose Present
When lactose is present, the lactose molecules bind to the repressor, changing the shape of the repressor.
The repressor molecule cannot bind to the operator, therefore, RNA polymerase CAN bind to the promoter and transcription does take place.
The enzymes needed to digest lactose are created.

31. Prokaryotic Regulation

32. Eukaryotic Regulation
Unlike prokaryotic cells, a variety of mechanisms regulate gene expression in eukaryotic cells:
Chromatin structure
Transcriptional control
Translational control

33. Eukaryotic Regulation
CHROMATIN STRUCTURE: Chromatin packing is used as a way to keep genes turned off.
If genes are not accessible to RNA polymerase, they cannot be transcribed.
In the nucleus, highly condensed chromatin is not available for transcription, while more loosely condensed chromatin is available for transcription.

34. Eukaryotic Regulation
TRANSCRIPTION FACTORS: DNA-binding proteins that help initiate transcription.
Transcription factors control the expression of genes (determine whether the gene should be shut off or turned on).

35. Eukaryotic Regulation
TRANSLATIONAL CONTROL: Occurs in the cytoplasm and affects when translation begins and how long it continues.
Example: Some mRNAs may need further processing before they are translated.

36. Cell Specialization
Eukaryotic cells have copies of all genes, however, different genes are expressed in different types of cells.
Example: Muscle cells have a different set of genes that are turned on than nerve cells.
Complex gene regulation in eukaryotes is what makes specialization possible.

37. Professor at Rockefeller
RNA Interference
Greg Hannon, PhD.
Cold Spring Harbor
Thomas Tushl, PhD.
Professor at Rockefeller

38. RNA Interference (micro RNA)
Cells contain lots of small RNA molecules
don’t belong to any of the major groups of RNA (mRNA, tRNA, or rRNA).
These small RNA molecules
play a powerful role in regulating gene expression by interfering with mRNA.

39. RNA Interference MicroRNA (miRNA), are small RNA molecules
regulate gene expression.
miRNA attach to certain mRNA molecules
prevent translation from occurring.

40. RNA Interference
Blocking gene expression by means of an miRNA silencing complex is known as RNA interference (RNAi).

41. The Promise of RNAi Technology
RNAi has made it possible to switch genes on and off by inserting double-stranded RNA into cells.

42. The Promise of RNAi Technology
RNAi technology may allow medical scientists to turn off the expression of genes
Cancer related diseases may be treated.

43. Genetic Control of Development
Gene expression shapes embryo development.
Every cell has the same genes, however, transcription factors and repressors determine which gene is turned on depending on the type of cell it is supposed to differentiate into.
The process of cells becoming specialized in structure and function is called differentiation.

44. Homeotic Genes: “Master Control Genes”
Control the identities of body parts in the embryo
Regulate organs that develop in specific parts of the body.

45. Homeobox and Hox Genes
Homeotic genes share a very similar 130-base DNA sequence, which was given the name homeobox.
Homeobox genes code for transcription factors that activate genes that are expressed in certain regions of the body.
They determine factors like the presence of wings or legs.

46. Homeobox and Hox Genes
A group of homeobox genes known as Hox genes are located side by side in a single cluster.
Hox genes determine the identities of each segment of an animal’s body.
Hox genes tell the cells of the body how to differentiate as the body grows.

47. Homeobox and Hox Genes
The colored areas on the fly show the approximate body areas affected by genes of the corresponding colors.
A mutation in one of these genes can completely change the organs that develop in specific parts of the body.
Clusters of Hox genes exist in the DNA of other animals, including humans.

48. Environmental Influences
Environmental factors like temperature, salinity, and nutrient availability can influence gene expression.
Example: The lac operon in E. coli
Metamorphosis is another example of how organisms can modify gene expression in response to their environment.
Example: Unfavorable conditions may force a frog to undergo metamorphosis faster than usual.