Topic 8 The control of gene expression Flashcards
(24 cards)
Inversion
A sequence of DNA bases/nucleotides detaches from the DNA sequence, then rejoins at the same position in the reverse order.
Explain how a gene mutation can lead to the production of the production of a non-functional protein or enzyme
- Changes sequence of base triplets of DNA so changes the sequence of codons of mRNA
- Changes sequence of amino acids in the encoded polypeptide
Changes position of hydrogen/ionic/disulphide bonds (between amino acids) - Changes tertiary structure of a protein
- Enzymes- active site changes shape so substrate cannot bind, enzyme-substrate complex can’t form
Explain why not all gene mutations affect the order of amino acids.
- some substitutions change only 1 triplet code/codon which could still code for the same amino acids
as the genetic code is degenerate - some occur in introns which do not code for amino acids as they are removed during splicing
Explain why a change in the amino acid sequence is not always harmful.
- may not change the tertiary structure of protein (if position of ionic/disulphide/hydrogen bonds don’t change)
- may positively change the properties of the protein, giving the organism a selective advantage
Explain what is meant by a frameshift
- occurs when mutations (A,D,D,T) change the no. of nucleotides/bases by a number not divisible by 3
- shifts how the genetic code is read, so all DNA triplets/mRNA codons downstream from the mutation change
Explain how mutations can lead to the production of shorter polypeptides
- deletion or translocation causes triplets/codons missing so amino acids are missing
- (S,A,D,D,I,T) premature stop triplet/codon so amino acids missing at the end of polypeptide
What are stem cells
Undifferentiated/unspecialised cells capable of
1. dividing by mitosis to replace themselves indefinitely
2. differentiating into other types of specialised cells
Describe how stem cells become specialised during development
- Stimuli lead to activation of some genes (due to transcription factors)
- So mRNA is transcribed only from these genes and translated to form proteins
- These proteins modify cells permanently and determine cell structure/function
Describe totipotent cells
- Occur for a limited time in early mammalian embryos
- Can divide and differentiate into any type of body cell (inc. extra-embryonic cells)
Describe pluripotent cells
- Found in mammalian embryos
- Can divide and differentiate into most cell types
Describe multipotent cells
- Found in mature mammals
- Can divide and differentiate into a limited number of cell types
Explain how stem cells can be used in the treatment of human disorders
- Transplanted into patients and divide in unlimited numbers
- Then differentiate into required healthy cells (to replace faulty/damaged calls)
Potential treatment of Type 1 diabetes by creating healthy islet cells that produce insulin
Bone marrow stem cell transplant for sickle cell disease / blood cancers
- Destroy patient’s bone marrow before treatment -> so no faulty cells are produced
- Transplant stem cells from healthy person -> divide and differentiate into healthy dells
Explain how induced pluripotent stem (iPS) cells are produced
- Obtain adult somatic (body) cells (non-pluripotent cells or fibroblasts) from patient
- Add specific protein transcription factors associated with pluripotency to cells so they express genes associated with pluripotency (reprogramming)
Transcription factors attach to promoter regions of DNA, stimulating or inhibiting transcription - Culture cells to allow them to divide by mitosis
Evaluate the use of stem cells in treating human disorders
For:
1. Can divide and differentiate into required healthy cells, so could relieve human suffering by saving lives and improving quality of life
2. Embryos are often left over from IVF and so would otherwise be destroyed
3. iPS cells unlikely to be rejected by patient’s immune system as made with patient’s own cells
4. iPS cells can be made without destruction of embryo and adult can give permission
Against:
1. Ethical issues with embryonic stem cells as obtaining them requires destruction of an embryo and potential life (embryo cannot consent)
2. Immune system could reject cells and immunosuppressant drugs are required
3. Cells could divide out of control, leading to formation of tumours / cancer
What are transcription factors?
- Proteins which regulate (stimulate or inhibit) transcription of specific target genes in eukaryotes
- By binding to a specific DNA base sequence on a promoter region (before/upstream of target gene)
- This stimulates or inhibits transcription (production of mRNA) of target genes by helping or preventing RNA polymerase from binding
Explain how oestrogen affects transcription
- Oestrogen is a lipid-soluble steroid hormone so diffuses into cell across the phospholipid bilayer
- In cytoplasm, oestrogen binds to its receptor, an inactive transcription factor, forming an oestrogen-receptor complex
- This changes the shape of the inactive transcription factor, forming an active transcription factor
- The complex diffuses from cytoplasm into the nucleus
- Then binds to a specific DNA base sequence on the promoter region of a target gene
- Stimulating transcription of target genes forming mRNA by helping RNA polymerase to bind
Explain why oestrogen only affects target cells
Other cells do not have oestrogen receptors
Describe what is meant by epigenetics
- Heritable changes in gene function/expression without changes to the base sequence of DNA
- Caused by changes in the environment
Describe what is meant by epigenome
All chemical modification of DNA and histone proteins -methyl groups on DNA and acetyl groups on histones
Explain how methylation and acetylation can inhibit transcription
- Increased methylation of DNA - methyl groups added to cytosine bases in DNA
- So nucleosomes (DNA wrapped around histone) pack more tightly together
- Preventing transcription factors and RNA polymerase binding to the promoter
- Decreased acetylation of histones increases positive charge of histones
- So histones bind DNA (negatively charged) more tightly
- Preventing transcription factors and RNA polymerase binding to promoter
Explain the relavance of epigenetics on disease development and treatment
Environmental factors (eg. diet, stress, toxins) can lead to epigenetic changes
These can stimulate / inhibit expression of certain genes that can lead to disease development
- Increased methylation of DNA OR decreased acetylation of histones inhibits transcription
- Decreased methylation of DNA OR increased acetylation of histones stimulates transcription
Diagnostic tests can be developed that detect these epigenetic changes before symptoms present
Drugs can be developed to reverse these epigenetic changes
What is RNA interference (RNAi)
- Inhibition of translation of mRNA produced from target genes, by RNA molecules
- This inhibits expression of silencing a target gene
Describe the regulation of translation by RNA interference
- Small interfering RNA (SiRNA) or micro-RNA (miRNA) is incorporated into/ binds to a protein, forming an RNA-induced silencing complex (RISC)
- siRNA synthesised as double-stranded RNA -> 1 strand incorporated
- miRNA synthesised as a double-stranded hairpin bend of RNA -> both strands incorporated - Single-stranded miRNA / siRNA within RISC binds to target mRNA with a complementary base sequence
- This leads to hydrolysis of mRNA into fragments which are then degraded OR prevents ribosomes binding
- Reducing/preventing translation of target mRNA into protein
