6.1.1: Genetics - Cellular control Flashcards
Mutation
A change to the sequence of nucleotides in DNA. Can be the arrangement of bases in an individual gene or structure of a chromosome.
Types of mutations
- Point mutation
- Chromosomal mutation
- Whole chromosome mutation
What is a point mutation?
when a single base is substituted, inserted or deleted.
Effect of a point mutation?
- Can lead to different amino acid (mis-sense mutation)
* Can change protein greatly (e.g. +ve charged amino acid ends up -ve)
Example of a mis-sense mutation
Sickle cell disease
• Mutation in haemoglobin gene
⟶ Hydrophilic glutamic acid replaced by hydrophobic valine
• Haemoglobin aggregates which distorts shape of RBC and decreases flexibility
Silent mutation
- 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.
How is a silent mutation possible?
Due to the degenerate nature of the genetic code
What are the types of point mutation?
- Mis-sense mutation
- Silent mutation
- Frameshift mutation
- Non-sense mutation
What is a frameshift mutation?
- type of point mutation
* deletion or insertion of a nucleotide results in a frameshift: every codon from that point on is different.
How does a frameshift mutation occur?
Occurs because bases are read in triplets
–> subsequent bases shifted forward/backward by one
Give an example of a disease caused by a frameshift mutation
- 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
What is a nonsense mutation?
- 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
What is a chromosomal mutation?
- gene deletion (can be beneficial/harmful)
- gene duplication (can be beneficial/harmful)
- inversion (genes swap places)
- translocation
Why could gene inversion be harmful?
- 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
What is translocation?
When whole sections of chromosomes swap/attach to other chromosomes
What is a whole chromosome mutation?
An entire chromosome is lost or repeated during cell division.
Give an example of a whole chromosome mutation
Downs Syndrome = extra chromosome 21
Autosome
non-sex chromosome
Possible effects of mutations
- Production of new/superior protein
- No effect
- Production inferior/no protein
Causes of mutations
- Can occur by mistake in DNA replication
- When DNA polymerase makes mistake
- Can spontaneously occur
- Can be caused by mutagens
Somatic mutations are…
in non-gamete cells and not inherited by offspring.
Mutagen
An agent (e.g. magnetic agent) that can increase the frequency of mutations above the naturally occurring rate
Examples of mutagens
- 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
Gene regulation (describe)
- Not all genes expressed in all cells
* Genes can be up- or down-regulated
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)
Exons
coding areas of DNA
Introns
non-coding, sometimes regulatory regions of DNA; removed from RNA in splicing so not in final mRNA
Heterochromatin
- Tightly coiled DNA (present during cell division)
* No transcription possible –> cannot access the gene
Euchromatin
- Loosely wound DNA (in interphase)
- Can be freely transcribed
- How tightly wound = how much gene needs to be expressed
Which genes are easily accessible (in the nucleus, considering hetero/euchromatin)
Housekeeping genes: genes needed for the running of the cell
Methods of transcriptional control
- Histone modification
* DNA modification
Methods of histone modification
- Acetylation
- Phosphorylation
- Methylation
Acetylation
- Addition of acetyl groups to histones
* Makes histones more negative –> DNA coils less tightly (∵ phosphates of DNA backbone = negative)
Phosphorylation
- Addition of phosphate groups to histones
* Makes histones more negative –> DNA coils less tightly (∵ phosphates of DNA backbone = negative)
Methylation
- Addition of methyl groups to histones
* Makes histones more hydrophobic so DNA coils more tightly
DNA modification
DNA itself can be methylated/acetylated to influence gene expression
Types of genes
- Regulatory genes
* Structural genes
Regulatory genes
Products = transcription factors or repressor proteins; regulate the expression of other genes
Structural genes
Product does not have a regulatory role
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
Operon
- group of genes that are under control of the same regulatory mechanism and are expressed at the same time.
- Only in prokaryotes
Lactose
- Disaccharide made of glucose and galactose
* Inducer of the lac operon
Inducer
- Substance which induces the transcription of genes
* (for the lac operon) Lactose
Regulator gene
• Codes for the repressor protein (which binds to the operator)
β-galactosidase
enzyme that hydrolyses lactose into glucose + galactose
Lactose permease
protein that forms channels allowing more lactose to enter the cell.
Structural genes
genes that code for the proteins β-galactosidase and lactose permease
Operator region
binding site for the repressor protein
Promotor region
binding site for RNA polymerase
RNA polymerase
enzyme that catalyses the formation of phosphodiester bonds between adjacent RNA nucleotides
Repressor protein
Stops transcription occurring by binding to the operator
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.
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
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
Effect of RNA editing
Increase range of proteins that can be produced from a single mRNA molecule
Epigenetics
the control of gene expression by the modification of DNA; sometimes includes all the ways gene expression is regulated
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.
Methods of translational control
- Degradation of mRNA
- Binding of inhibitory proteins to mRNA
- Activation of initiation factors
Degradation of mRNA
more resistant –> lasts longer –> greater quantity of protein synthesised
Binding of inhibitory proteins to mRNA
prevents mRNA binding to ribosome
Activation of initiation factors
aid binding of mRNA to ribosome
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
Protein kinases
enzymes that catalyse the addition of phosphate groups to proteins; alters 3° structure and therefore function
⟶ Many enzymes activated by phosphorylation
What do you call mRNA that stills contains introns?
Primary mRNA
What do you call mRNA that has had introns removed?
Mature mRNA
3 processes that are involved in producing whole organism (from fertilised egg)?
- Cell division
- Cell differentiation
- Morphogenesis
What is morphogenesis?
Spatial distribution of cells
Describe embryonic stem cells
Totipotent: undifferentiated and can form any cell
Differentiation
The process by which cells become differentiated.
Pattern formation
The development of a spatial organisation in which an organism’s tissues and organs are all in their characteristic places.
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)
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)
Homeobox genes contain
• 180bp sequence called the homeobox
Homeobox encodes
a 60 amino acid sequence (the homeodomain)
Homeodomain
- The 60 amino acid sequence encoded for by the 180bp homeobox sequence of a homeobox gene
- The homeodomain binds to DNA
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
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
Homeobox genes in which kingdoms are highly conserved?
- Animals
- Fungi
- Plants
Apoptosis
programmed cell death that occurs in multicellular organisms
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
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
Why apoptosis is important
Needed to destroy:
• Cells infected with viruses
• Cells with DNA damage
• Cancer cells
• Also needed for proper development
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
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)
Too much apoptosis results in…
Tissue atrophy
Neurodegeneration
Thin skin
Too little apoptosis results in…
Hyperplasia
Cancer
Mitosis and apoptosis are regulated by…
Hox genes
Apoptosis can be influenced by…
internal and external factors (different types of stress)
⟶ External: change in temp., light intensity
⟶ Internal: hormones, psychological stress
