6.1.1: Genetics - Cellular control Flashcards
1
Q
Mutation
A
A change to the sequence of nucleotides in DNA. Can be the arrangement of bases in an individual gene or structure of a chromosome.
2
Q
Types of mutations
A
- Point mutation
- Chromosomal mutation
- Whole chromosome mutation
3
Q
What is a point mutation?
A
when a single base is substituted, inserted or deleted.
4
Q
Effect of a point mutation?
A
- Can lead to different amino acid (mis-sense mutation)
* Can change protein greatly (e.g. +ve charged amino acid ends up -ve)
5
Q
Example of a mis-sense mutation
A
Sickle cell disease
• Mutation in haemoglobin gene
⟶ Hydrophilic glutamic acid replaced by hydrophobic valine
• Haemoglobin aggregates which distorts shape of RBC and decreases flexibility
6
Q
Silent mutation
A
- type of point mutation
- when the substitution of a base still codes for the same amino acid as the original base.
- Mutation has no effect on production of final polypeptide.
7
Q
How is a silent mutation possible?
A
Due to the degenerate nature of the genetic code
8
Q
What are the types of point mutation?
A
- Mis-sense mutation
- Silent mutation
- Frameshift mutation
- Non-sense mutation
9
Q
What is a frameshift mutation?
A
- type of point mutation
* deletion or insertion of a nucleotide results in a frameshift: every codon from that point on is different.
10
Q
How does a frameshift mutation occur?
A
Occurs because bases are read in triplets
–> subsequent bases shifted forward/backward by one
11
Q
Give an example of a disease caused by a frameshift mutation
A
- Tay-Sachs disease
- Deletion mutation
- Autosome recessive disorder
- Prevents enzyme to break down lipids from working –> lipids accumulate in brain –> mental and physical activity decline to death at 4 y.o.
- No cure
12
Q
What is a nonsense mutation?
A
- substitution of base occurs leading to premature ‘stop’ codon
- Premature end to synthesis of polypeptide –> almost certainly unable to function as protein
- Type of point mutation
13
Q
What is a chromosomal mutation?
A
- gene deletion (can be beneficial/harmful)
- gene duplication (can be beneficial/harmful)
- inversion (genes swap places)
- translocation
14
Q
Why could gene inversion be harmful?
A
- Inversion: genes swap places
- Could affect gene activation
- e.g. A is expected but B is produced
- Produce genes at the wrong time/in wrong cell
15
Q
What is translocation?
A
When whole sections of chromosomes swap/attach to other chromosomes
16
Q
What is a whole chromosome mutation?
A
An entire chromosome is lost or repeated during cell division.
17
Q
Give an example of a whole chromosome mutation
A
Downs Syndrome = extra chromosome 21
18
Q
Autosome
A
non-sex chromosome
19
Q
Possible effects of mutations
A
- Production of new/superior protein
- No effect
- Production inferior/no protein
20
Q
Causes of mutations
A
- Can occur by mistake in DNA replication
- When DNA polymerase makes mistake
- Can spontaneously occur
- Can be caused by mutagens
21
Q
Somatic mutations are…
A
in non-gamete cells and not inherited by offspring.
22
Q
Mutagen
A
An agent (e.g. magnetic agent) that can increase the frequency of mutations above the naturally occurring rate
23
Q
Examples of mutagens
A
- High energy radiation: x-rays, gamma rays, UV light
- Chemicals: tars and others in cigarettes
- Viruses: e.g. HPV –> cervical cancer
- Free radicals: can disrupt base pairing in replication
24
Q
Gene regulation (describe)
A
- Not all genes expressed in all cells
* Genes can be up- or down-regulated
25
Ways in which genes can be regulated
1) Transcriptional control
2) Post-transcriptional control/modification of mRNA to regulate translation
3) Translational control
4) Post-translational control (protein modification)
26
Exons
coding areas of DNA
27
Introns
non-coding, sometimes regulatory regions of DNA; removed from RNA in splicing so not in final mRNA
28
Heterochromatin
* Tightly coiled DNA (present during cell division)
| * No transcription possible --> cannot access the gene
29
Euchromatin
* Loosely wound DNA (in interphase)
* Can be freely transcribed
* How tightly wound = how much gene needs to be expressed
30
Which genes are easily accessible (in the nucleus, considering hetero/euchromatin)
Housekeeping genes: genes needed for the running of the cell
31
Methods of transcriptional control
* Histone modification
| * DNA modification
32
Methods of histone modification
* Acetylation
* Phosphorylation
* Methylation
33
Acetylation
* Addition of acetyl groups to histones
| * Makes histones more negative --> DNA coils less tightly (∵ phosphates of DNA backbone = negative)
34
Phosphorylation
* Addition of phosphate groups to histones
| * Makes histones more negative --> DNA coils less tightly (∵ phosphates of DNA backbone = negative)
35
Methylation
* Addition of methyl groups to histones
| * Makes histones more hydrophobic so DNA coils more tightly
36
DNA modification
DNA itself can be methylated/acetylated to influence gene expression
37
Types of genes
* Regulatory genes
| * Structural genes
38
Regulatory genes
Products = transcription factors or repressor proteins; regulate the expression of other genes
39
Structural genes
Product does not have a regulatory role
40
Why does the lac operon give E. coli a selective advantage?
* Bacteria are able to utilise an alternative food source when glucose isn't available
* Bacteria don't waste energy producing enzyme needed to break down lactose if it isn't present
* Bacteria can't produce enzyme (β-galactosidase) unless lactose is present in the environment
41
Operon
* group of genes that are under control of the same regulatory mechanism and are expressed at the same time.
* Only in prokaryotes
42
Lactose
* Disaccharide made of glucose and galactose
| * Inducer of the lac operon
43
Inducer
* Substance which induces the transcription of genes
| * (for the lac operon) Lactose
44
Regulator gene
• Codes for the repressor protein (which binds to the operator)
45
β-galactosidase
enzyme that hydrolyses lactose into glucose + galactose
46
Lactose permease
protein that forms channels allowing more lactose to enter the cell.
47
Structural genes
genes that code for the proteins β-galactosidase and lactose permease
48
Operator region
binding site for the repressor protein
49
Promotor region
binding site for RNA polymerase
50
RNA polymerase
enzyme that catalyses the formation of phosphodiester bonds between adjacent RNA nucleotides
51
Repressor protein
Stops transcription occurring by binding to the operator
52
Lac operon steps
1) Repressor protein bound to operator, preventing transcription of genes Z and Y. Lactose conc. = low
2) When lactose conc. = high, lactose binds t repressor protein at its other binding site
3) When lactose binds to repressor protein, latter's shape changes so it can no longer bind to the operator.
4) Repressor protein dissociates from the operator; transcription of genes Z and Y is now possible.
5) RNA polymerase binds to the promoter, catalyses the formation of phosphodiester bonds between adjacent RNA nucleotides in transcription.
6) An mRNA copy of the genes is produced.
7) This mRNA is translated into a sequence of amino acids by a ribosome
8) Gene Z codes for β-galactosidase. Gene Y codes for lactose permease.
9) After translation, chains of amino acids move away from ribosome, fold into proteins.
10) β-galactosidase hydrolyses lactose into glucose + galactose. Lactose permease forms channels that make the cell more permeable to lactose.
53
Explain why β-galactosidase and lactose permease are not produced when lactose is absent
* Repressor protein is bound to the operator, blocking binding site for RNA polymerase
* This saves energy/amino acids/resources
54
Methods of RNA processing
* Cap (modified nucleotide) added to 5' end
* Tail (chain of adenine nucleotides) added to 3' end
* Splicing: introns removed
* RNA editing: base addition, deletion, substitution
55
Effect of RNA editing
Increase range of proteins that can be produced from a single mRNA molecule
56
Epigenetics
the control of gene expression by the modification of DNA; sometimes includes all the ways gene expression is regulated
57
Role of cAMP in the lac operon
• Increases rate of transcription (up-regulates)
* Binds to CRP protein which then binds to 2nd binding site on the promoter
* cAMP levels in the E.Coli are low when glucose is transported in. Thus when glucose is being used as a respiratory substrate, genes associated with lactose aren’t transcribed.
58
Methods of translational control
* Degradation of mRNA
* Binding of inhibitory proteins to mRNA
* Activation of initiation factors
59
Degradation of mRNA
more resistant --> lasts longer --> greater quantity of protein synthesised
60
Binding of inhibitory proteins to mRNA
prevents mRNA binding to ribosome
61
Activation of initiation factors
aid binding of mRNA to ribosome
62
Methods of post-translational control
* Addition of non-protein groups
* Modifying amino acids, formation of bonds
* Folding/shortening of protein
* Modification by cAMP
* Protein kinases
63
Protein kinases
enzymes that catalyse the addition of phosphate groups to proteins; alters 3° structure and therefore function
⟶ Many enzymes activated by phosphorylation
64
What do you call mRNA that stills contains introns?
Primary mRNA
65
What do you call mRNA that has had introns removed?
Mature mRNA
66
3 processes that are involved in producing whole organism (from fertilised egg)?
* Cell division
* Cell differentiation
* Morphogenesis
67
What is morphogenesis?
Spatial distribution of cells
68
Describe embryonic stem cells
Totipotent: undifferentiated and can form any cell
69
Differentiation
The process by which cells become differentiated.
70
Pattern formation
The development of a spatial organisation in which an organism's tissues and organs are all in their characteristic places.
71
Why use Drosophila to study body plans?
* Reproduce quickly
* Segmented bodies
* Small (can keep many)
* Cheap
* Low maintenance
* Sexually dimorphic (easy to tell male from female)
72
Homeobox genes (types)
* Maternal effect genes (already present in egg)
* Segmentation genes (specify polarity of each segment)
* Homeotic selector genes (specify the development of each section i.e. appendages)
73
Homeobox genes contain
• 180bp sequence called the homeobox
74
Homeobox encodes
a 60 amino acid sequence (the homeodomain)
75
Homeodomain
* The 60 amino acid sequence encoded for by the 180bp homeobox sequence of a homeobox gene
* The homeodomain binds to DNA
76
Why are homeobox genes highly conserved?
* These genes are very important
* Any mutation will have large effects, altering the body plan
* Any mutation is likely to be lethal/selected against
77
What is a homeobox gene?
A regulatory homeotic gene
Contains 180 base pair homeobox sequence that codes for homeodomain (protein) which binds to DNA --> controls development of body plan
78
Homeobox genes in which kingdoms are highly conserved?
* Animals
* Fungi
* Plants
79
Apoptosis
programmed cell death that occurs in multicellular organisms
80
Apoptosis vs. necrosis
```
NECROSIS
• Passive
• Pathological
• Involves swelling, lysis of cells; inflammation
• Externally induced
```
```
APOPTOSIS
• Active
• Physiological or pathological
• Chromatin is condensed, cytoplasm becomes dense
• Vesicles engulfed by phagocytosis
• Internally or externally induced
```
81
Apoptosis process
* Cytoskeleton broken down by enzymes
* Cell shrinks causing cytoplasm to become more dense w/ tightly packed organelles
* Chromatin condenses and nuclear envelope breaks down
* Cell surface changes and small parts form blebs
* Vesicles engulfed by phagocytosis
82
Why apoptosis is important
Needed to destroy:
• Cells infected with viruses
• Cells with DNA damage
• Cancer cells
• Also needed for proper development
83
Apoptosis as needed for proper development (examples)
* Reabsorption of tadpole tail
* Formation of fingers and toes of foetus
* Sloughing off of uterus lining
* Formation of proper connections between neurones in the brain
84
Apoptosis for continuing body development
* Organ size (eliminates excess cells)
* Immunity (eliminates dangerous cells)
* Tissue remodelling (eliminates cells no longer needed)
* Selection (eliminates cells no longer needed)
85
Too much apoptosis results in...
Tissue atrophy
Neurodegeneration
Thin skin
86
Too little apoptosis results in...
Hyperplasia
| Cancer
87
Mitosis and apoptosis are regulated by...
Hox genes
88
Apoptosis can be influenced by...
internal and external factors (different types of stress)
⟶ External: change in temp., light intensity
⟶ Internal: hormones, psychological stress
