Cellular control Flashcards
What is a mutation
A random change to the genetic material - (DNA)
When do gene mutations occur
Spontaneously during DNA replication before mitosis
What can cause gene mutations
Certain chemicals i.e. tar in tobacco smoke, ionising radiation (UV light, X-rays, gamma rays)
What is the difference between mutations in mitosis compared to mutations in meiosis
Mitosis (somatic mutation) not passed onto offspring
Meiosis - may be inherited by offspring
What are the two main classes of DNA mutation
Point mutation: one base pair replaces (is substituted) for another
Indel mutations: Both insertions/deletions cause a frameshift
What are the three types of point mutations
-Silent
-Missense
-Nonsense
What reduces the chance of a mutations
The genetic code is degenerate - amino acids have more than one base triplet code
Silent mutations
A change in the base triplet, where the triplet still codes for the same amino acid
-The primary/secondary/tertiary structure remains unaltered
Missense mutations
A change to the base triplet sequence that leads to a change in the amino acid sequence of a protein
-Alters the primary structure thus the tertiary structure is altered and the protein will no longer be able to perform its function
Example of a missense mutation
Sickle cell anaemia - Valine on the sixth base triplet instead of glutamic acid is inserted
-Results in deoxygenated haemoglobin crystallising within erythrocytes, causing them to become sickle-shaped, which blocks capillaries and deprives tissues of O2
When may missense mutations not matter
-When the changed amino acid has a similar R group/ codon to the original
- If the changed amino acid does not make up part of the proteins active site so the protein can still perform its function
Nonsense mutations
May alter a base triplet so it becomes a termination (stop) triplet
-Results in a truncated protein that will not function
-Degraded within the cell
What disease is the result of nonsense mutations
Duchenne muscular dystrophy
What do indel mutations involve
- Insertion/deletion of a base that causes a frameshift
- Can cause expanding triplet nucleotide repeats
Insertions/deletions
- If nucleotide base pairs (not in multiples of threes) are inserted in the gene/ deleted from the gene as the code is non-overlapping and read in codons all the subsequent base triplets will be altered
-The primary and subsequently the tertiary structure will be altered and the protein will not be able to perform its function
What happens if the protein is very abnormal
It is rapidly degraded within the cell
What diseases can occur due to insertions/ deletions
thalassaemia - a haemoglobin disorder
Why is the insertion/deletion of a triplet of base pairs not an indel mutation
Results only in the gain/loss of an amino acid and not in a frame shift
Expanding triplet repeats
Amino acid triplet repeats ( - CAG,CAG,CAG-) increase in meiosis through each generation
- Five repeats could be inserted in one division and then in the next another three are added etc.
What disease occurs due to expanding triplet repeats
Huntington’s disease - when repeats go above a critical number
Why are all mutations not harmful
Some are beneficial and have helped drive evolution through natural selection.
-Different alleles of the same gene are provided via mutation
What mutations in humans are neither beneficial or harmful
- Inability to smell certain flowers i.e. freesias and honeysuckle
-Different shaped earlobes
Name the different parts of the lac operon and their function
(The control region)
Promoter region - where RNA polymerase binds to begin transcription
lac O (operator region) - Binds to the repressor gene
Name the different parts of the lac operon and their function
(Structural genes)
lac z - transcribes mRNA that will translate B galactosidase
lac y - transcribes mRNA that will translate lactose permease
B galactosidase function
Hydrolyses lactose to glucose and galactose
Lactose permease function
Allows lactose to enter the bacterial cell
Regulator gene I function
Not part of the lac operon
When switched on codes for the repressor gene
What happens on the lac operon when glucose is present
(E-coli)
1) Regulator gene I is expressed and a repressor protein is produced
2) Repressor protein binds to the operator (lac O) and prevents RNA from binding to the promoter region
3) Repressor protein prevents lax Z and lac Y from being expressed so enzymes for lactose metabolism are not made (genes are switched off)
4) This prevents waste of amino acids and energy as e-coli can respire the glucose
What happens on the lac operon when lactose is present (E-coli)
1) When lactose is added to the culture medium lactose binds to the repressor protein
2) This alters the repressor proteins shape and it can no longer bind to the operator region
3) RNA polymerase can bind to the promoter and begin to transcribe the structural genes into mRNA that will translate the two enzymes
4)E-coli can increase the uptake of lactose as it can induce enzymes to break itself down
What is the advantage of the lac operon system in e-coli only inducing the enzymes when lactose is present
It does not waste amino acids and energy to induce the production of enzymes to break down lactose as it can respire glucose when it is present and they are not needed
What is a transcription factor
A protein/ short non-coding piece of RNA
What does the transcription factor do
An extra step in eukaryotes in transcription
-Once its bound to the promoter it makes it either easier/harder for RNA polymerase to bind to the promoter
-Transcription factor /s either activates or suppresses transcription of the structural gene
Transcription in eukaryotes when transcription factor activates transcription of the structural gene
1) Promoter and structural gene
2) Transcription factor binding to the promoter
3) RNA polymerase also attaches to the promoter and transcription of the structural gene can begin
Transcription in eukaryotes when transcription factor suppresses transcription of the structural gene
1) Promoter and structural gene
2) Transcription factor binding to the promoter
3) RNA polymerase cannot attach to the promoter as the transcription factor suppresses the transcription of the structural gene as it inhibits the RNA polymerase from binding
What does post-transcriptional gene regulation involve
Introns and exons
Introns
Noncoding region of DNA; sequence of nucleotides within a gene that does not remain in the mRNA transcribed from that gene
Exons
The coding, or expressed region of DNA; a nucleotide sequence within a gene that remain in the final mRNA transcribed from that gene
Post-transcriptional gene regulation - what happens?
1) Both introns and exons are transcribed from DNA, resulting in primary mRNA
2) The introns are then removed and the exons are joined together
3) Resulting in mRNA (exons) and introns are used as transcription factors or to encode proteins
What is mRNA called with both introns and exons
Primary mRNA
What enzymes are involved in the editing and splicing process
Endonuclease
What can DNA do depending on how it is spliced
Encode for more than one protein
What does post-translational level of gene regulation involve
Involves the activation of proteins
How are enzymes activated
By being phosphorylated
How does cAMP activate enzymes and also may help stimulate transcription
1-4 (to the formation of cAMP)
1) A signalling molecules such as glucagon, bind to receptor on plasma membrane of the target cell
2) Activates G protein
3) G protein activates adenyl cyclase
4) Activated adenyl cyclase enzymes catalyse the formation of many molecules of cAMP from ATP
How does cAMP activate enzymes and also may help stimulate transcription (5-6)
5) cAMP activates PKA (protein kinase A)
6) Activated PKA catalyses the phosphorylation of various proteins, hydrolysing ATP in the process. This phosphorylation activates many enzymes in the cytoplasm i.e. those that convert glycogen to glucose
How does cAMP activate enzymes and also may help stimulate transcription (7-8)
What can the activated protein PKA also do
7) PKA may also phosphorylate another protein (CREB)
8) This then enters the nucleus and acts as a transcription factor to regulate transcription
Apoptosis
Programmed cell death
Process of apoptosis - what happens?
1-6
1) Enzymes break down cell cytoplasm
2) The cytoplasm becomes dense with tightly packed organelles
3) The plasma membrane changes and small protrusions called blebs form
4) Chromatin condenses, the nuclear envelope breaks and DN breaks into fragments
5) The cell breaks into vesicles that are ingested by phagocytic cells; so that cell debris does not damage any other cells/tissues
6) The whole process happens quickly
What helps to control apoptosis
Cell signalling molecules - respond to both external and internal cell stimuli i.e. stress
Plays a crucial role in making sure the right amount of apoptosis occurs
Examples of cell signalling molecules that help to control apoptosis
Cytokines, hormones, growth factors, nitric oxide
Nitric oxide - what does it do?
Can induce apoptosis by making the inner mitochondrial membrane more permeable to hydrogen ions and removing the proton gradient
-The proteins are then released into the cytoplasm and bind to apoptosis inhibitor proteins, which allows apoptosis to occur
Benefits of apoptosis
-Can prevent the extensive proliferation of cells, without needing the release of hydrolytic enzymes, which can damage cell tissue
-During limb development, apoptosis causes the digits to separate from each other
-Removes ineffective/harmful T lymphocytes during the development of the immune system
How much should apoptosis occur and what happens if there is too much/too little of it
The rate of cells dying = The rate of cells produced by mitosis
- Not enough apoptosis leads to the formation of tumours
-Too much apoptosis leads to cell loss and degeneration
Cell signalling plays a crucial role in maintaining the right balance
How does apoptosis differ from necrosis
Necrosis is caused by trauma i.e. pathogens
- Releases hydrolytic enzymes = can damage other cells
What are homeotic genes
The genes in DNA that regulate morphogenesis
What is morphogenesis
The process that causes an organism to form its shape
What is a subset of homeotic genes called
Homeobox genes = codes for the protein
What is the homeobox sequences
Part of the homeobox gene is an 180 base pair length of DNA
What does a homeobox do
Codes for a specific sequence of 60 amino acids, within the synthesised protein, called a homeodomain
The homeodomain
What the homeobox codes for
-folds into a specific shape consisting of three alpha helices
-2nd and 3rd helix create a helix turn helix
Helix turn helix
2nd and 3rd alpha helices are connected by a short loop of amino acids
Purpose of the helix turn helix
Allows the protein to bind to DNA and regulate the transcription of nearby genes
- Proteins that contain homeodomains are therefore transcription factors
Purpose of homeodomain
Binds to the DNA and acts as a transcription factor and therefore regulates other genes being switched on
What are hox genes
Homeobox genes in animals
- Involved in the formation of anatomical features in the correct locations of the body plan
What kind of animals are hox genes found in and what does this suggest
Bilaterian animals = suggest hox genes must have existed in the common ancestor of all bilaterians
How are the hox genes arranged
Several hox genes are found next to each other on a chromosome and are arranged in clusters
What is a homeotic mutation
When a hox gene is mutated body parts develop on the wrong places of the body
When are hox genes expressed
In early embryonic development along the anterior-posterior (head-tail) axis of the organism
Spatial linearity
The order of the genes on the chromosome matches the expression pattern along the embryo
- the genes for the head are found first
Temporal order
The genes for the head are expressed first
Collinearity
Spatial linearity + temporal order
-Scientists do not yet understand the importance of this for hox genes
What happens when each hox gene is expressed
It encodes a specific hox protein that acts as a transcripton factor
What do activated genes promote
The correct development of each body segment by regulating mitosis, apoptosis and cell differentiation
How are hox genes regulated
Gap genes and pair rule genes
-These are then regulated by maternally supplied mRNA from the egg cytoplasm
How does a STOP codon work
Does not for an amino acid/ no matching tRNA
Why does meiosis have two stages
-To halve chromosome no. = diploid to haploid
-Separate homologous pairs (of chromosomes) and sister chromatids
-Chromosomes are two chromatids to start
Why does the homeotic gene not really mutate
- Genes are very important
-Mutation would have large effects
-Many other genes affected
-Mutation = lethal
