Topic 8: The Control Of Gene Expression Flashcards
Define gene mutation
Changes in the DNA base sequence which can arise spontaneously during DNA replication
Define mutagenic agent
Factor that increases rate of mutation
Examples of mutagenic agent
UV light
Alpha particles
Explain how a gene mutation can lead to the production of a non-functional protein / enzyme
1) Sequence of base triplets in DNA change —> sequence of codons on mRNA change
2) So changes the sequence of amino acids in the encoded polypeptide
3) Which changes position of hydrogen / ionic / disulphide bonds between amino acids
4) This changes the tertiary structure of protein
5) Enzyme active sites change shape so substrates can’t bind —> no enzyme-substrate complexes form
What are the 6 types of mutations?
1) Substitution
2) Addition
3) Deletion
4) Duplication
5) Inversion
6) Translocation
Describe substitution
A base is replaced by a different base in DNA
Describe addition
1 or more bases are added to the DNA base sequence
Describe deletion
1 or more bases are lost from the DNA base sequence
Describe duplication
A sequence of DNA bases are repeated / copied
Describe inversion
Sequence of bases detached from the DNA sequence & rejoins at the same position in inverse order
Describe translocation
Sequence of DNA bases detaches and is inserted at a different location within the same (or different) chromosome
Why don’t all gene mutations affect the order of amino acids?
1) Some substitutions only change 1 triplet code (codon) which could still code for the same amino acid
—> As the code is degenerate
2) Some occur in introns which don’t code for an amino acid
Define degenerate
1 amino acid can be coded for by more than 1 triplet
Why aren’t changes in amino acid sequence always harmful?
1) May not change the tertiary structure of protein (if position of ionic / hydrogen / disulphide bonds don’t change)
2) May positively change properties of protein, giving the organism a selective advantage
Explain frame shift
1) Occurs when gene mutations change the number of nucleotides / bases by any number that isn’t divisible by 3
2) This shifts the way the genetic code is read, so all DNA triplets (or mRNA codons) downstream from the mutation gene
3) The sequence of amino acids encoded changes accordingly and the effects on the encoded polypeptide are significant
What happens if a multiple of 3 bases is added / removed?
No frame shift but will result in an extra / less amino acid in the encoded polypeptide
How can frame shift lead to a shorter polypeptide?
Produce a stop codon
Define a stem cell
Undifferentiated / unspecialised cell which can divide by mitosis and differentiate into other types of cells
How do stem cells become specialise during development?
1) Stimuli lead to activation of some genes
2) So mRNA is transcribed only from these genes and then translate to form proteins
3) These proteins modify cells permanently and determine the cell structure / function
Describe totipotent cells
1) Occur for limited time in early mammalian embryos
2) Can divide and differentiate into any type of body cell
Describe pluripotent cells
1) Found in mammalian embryos
2) Can divide and differentiate into most cell types
What is the only cell type in the body that isn’t pluripotent?
Placenta cells
Describe multipotent cells
1) Found in mature mammals
2) Can divide and differentiate into a limited number of cell types
Example of multipotent cells
Bone marrow
—> can divide and differentiate into different types of blood cells
Describe unipotent cells
1) Found in mature mammals
2) Can divide into just one type of cell
Example of unipotent cells
Unipotent cells in the heart can divide and differentiate into cardiomyocytes
How can stem cells be used to treat human disorders?
1) Transplanted into patients to divide in unlimited number
2) Then differentiate into required healthy cells
Examples of stem cells using in treatment of human disorders
1) Potential treatment in type 1 diabetes by creating healthy islet cells that produce insulin
2) Bone marrow stem cell transplant for SCD / blood cancers
—> Destroy patient bone marrow before treatment so no faulty cells are produced
—> Transplant stem cells from healthy person which divide and differentiate into healthy cells
What does iPS cells stand for?
Induced pluripotent stem cells
How are iPS cells produced?
1) Obtain adult somatic cells from patient
2) Add specific protein transcription factors associated with pluripotency to cells so they express genes associated with pluripotency
—> Transcription factors attach to promoter regions of DNA, stimulating / inhibiting transcription
3) Culture cells allow them to divide by mitosis
What happens once iPS cells are produced?
They can divide and differentiate into healthy cells to transplant into the same patient
What is the pathway for iPS cell production?
1) Somatic cells from patient + transcription factors —> iPS cells
2) iPS cells differentiate into specialised cells
3) Specialised cells are transplanted into patient
Positives for using stem cells in treating human disorders
1) Can divide and differentiate into required healthy cells —> relieve human suffering by saving lives and improving quality of life
2) Embryos often left over from IVF & are otherwise destroyed
3) iPS cells unlikely to be rejected by patient immune system as they made with the patients cells
4) iPS cells can be made without destruction of embryo and adult can give permission
Negatives for using stem cells in treating human disorders
1) Ethical issues with embryonic stem cells —> obtaining cells requires destruction of embryo & potential life
2) Immune system could reject cells and immunosuppressant drugs are required
3) Cells could divide out of control, leading to tumours / cancer
Describe transcription factors?
Proteins which regulate transcription of specific target genes in eukaryotes by binding to a specific DNA base sequence on a promoter region
Describe how transcription can be regulated using transcription factors
1) Transcription factors move from cytoplasm to nucleus
2) Binds to DNA at a specific DNA base sequence on a promoter region
3) This stimulates / inhibits transcription of target genes by helping / preventing RNA polymerase binding
How does oestrogen affect transcription?
1) Oestrogen = lipid soluble steroid hormone—> diffuses into cell across phospholipid bilayer
2) In cytoplasm, oestrogen binds to receptor (inactive transcription factor) forming and oestrogen-receptor complex
3) Changes shape of inactive transcription factor, forming and active transcription factor
4) Complex diffuses from cytoplasm into nucleus
5) Then binds to specific DNA base sequence in promoter region of target gene
6) Stimulating transcription of target genes forming mRNA by helping RNA polymerase to bind
Why does oestrogen only affect target cells?
Other cells don’t have oestrogen receptors
Define epigenetics
Heritable changes in gene function without changes to base sequence of DNA, caused by changes in the environment
Define epigenome
All chemical modification of DNA and histone proteins —> methyl groups in DNA and acetyl groups on histones
What happens to the methylation of DNA if transcription is inhibited?
Increases
What happens to methylation of DNA if transcription is allowed?
Decreases
What happens to acetylation of histones when transcription is inhibited?
Decreases
What happens to acetylation of histones if transcription is allowed?
Increases
How does methylation inhibit transcription?
1) Increased methylation of DNA –> methyl groups added to cytosine bases in DNA
2) So nucleosomes are packed more tightly together
3) Preventing transcription factors and RNA polymerase binding to promoter
How does acetylation inhibit transcription?
1) Decreased acetylation of histones increases positive charge of histones
2) So histones bind DNA more tightly
3) Preventing transcription factors and RNA polymerase binding to promoter
Relevance of epigenetics on disease development and treatment
1) Environmental factor (eg. Diet) can lead to epigenetic changes
2) These stimulate / inhibit expression of certain genes that can lead to disease development
–> Increased methylation of DNA / decreased acetylation of histones inhibits transcription
–> Decreased methylation of DNA / increased acetylation of histones stimulates transcription
3) Diagnostic tests can be developed that detect these epigenetic changes before symptoms present
4) Drugs can be developed to reverse these epigenetic changes
What is RNA interference?
Inhibition of mRNA produced from target genes, by RNA molecules –> inhibits depression of target gene
Where does RNA interference occur?
Eukaryotes and some prokaryotes
Describe the regulation of translation of RNA interference
1) Small interfering RNA (siRNA) / micro-RNA (miRNA) binds to a protein, forming and RNA-induced silence complex (RISC)
–> siRNA synthesised as double stranded RNA (1 strand incorporated)
–> miRNA synthesised as a double stranded hairpin bend of RNA (both strands incorporated)
2) Single-stranded miRNA / siRNA within RISC bings to target mRNA with complementary base sequence
3) Leads to hydrolysis of mRNA into fragments which are then degraded OR prevents ribosome binding
4) Reducing / preventing translation of target mRNA into protein
How do tumours and cancers form?
1) Mutations in DNA controlling mitosis can lead to uncontrolled cell division
2) Tumour is formed if this results in mass of abnormal cells
What are the types of tumours?
Malignant –> cancerous & can spread by metastasis
Benign –> non-cancerous
Main characteristics of benign tumours
1) Usually grow slowly
2) Cells are differentiated and specialised
3) Cells have normal nuclei
4) Well defined borders & often surrounded by a capsule –> so don’t invade surrounding tissue
5) Don’t spread by metastasis
6) Can normally be removed by surgery and rarely return
Why doe benign tumours not spread by metastasis?
Cell adhesion molecules stick cells together
Main characteristics of malignant tumours
1) Usually grow faster
2) Cells become poorly differentiated / unspecialised
3) Cells have irregular, larger nuclei
4) Poorly defined borders & not encapsulated –> can invade surrounding tissue
5) Spread by metastasis –> cells break off and spread to other parts of the body, forming secondary tumours
6) Can normally be removed by surgery combined with radiotherapy / chemotherapy but often return
Describe the function of tumour suppressor genes
Code for proteins that inhibit / slow the cell cycle OR causes self-destruction of potential tumour cells
