[In Progress][Y2] The Control of Gene Expression Flashcards
What is gene mutation?
Any change to one or more nucleotide bases, or any rearrangement of the bases, in DNA.
List the different types of mutation.
- Substitution
- Deletion
- Addition
- Duplication
- Inversion
- Translocation
What is meant by a substitution mutation?
Where a section of a DNA molecule is replaced by another nucleotide that has a different base.
What are the consequences of a substitution mutation?
- Could form a stop codon, so will result in the polypeptide being produced to end prematurely. The final protein will almost certainly not perform its normal function.
- Could form a codon for a different amino acid. This would affect the primary structure of the protein, which may change the shape of the tertiary structure of the protein.
- Could form a codon that results in the same amino acid as before. This is because code is degenerate, so will have no effect.
What is meant by a deletion mutation?
The loss of a nucleotide base from a DNA sequence.
What are the consequences of a deletion mutation?
- Results in a frame-shift to the left by one.
- This means the gene is now read in the wrong three bases, and so all amino acids coded for after the frame-shift, are likely to be incorrect, resulting in a different polypeptide.
- This non-functional polypeptide could lead to considerable alterations of the phenotype.
- Thus a deleterious base at the start is more detrimental to one at the end.
What is meant by an addition mutation?
When an extra base becomes inserted into a sequence of DNA.
What are the consequences of an additon mutation?
- Results in a frame-shift to the right by one.
- If three extra bases are added, and any multiple of three there is no frame-shift.
- The resulting polypeptide will be different than if no mutation was present, but it will not be to the same extent of one with a frame shift.
What is meant by a duplication mutation?
One or more bases are repeated.
What are the consequences of a duplication mutation?
Frame shift to the right.
What is meant by an inversion mutation?
A group of bases become separated from the DNA sequence and rejoin at the same position but in the reverse order.
What are the consequences of an inversion mutation?
The base sequence is reversed and will affect the primary structure of the polypeptide.
What is meant by a translocation mutation?
A group of bases becoming separate from the DNA sequence of a different chromosome and is inserted into the base sequence of a different chromosome.
What are the consequences of a translocation mutation?
Can lead to an abnormal phenotype, including the development of certain forms of cancer and reduced fertility.
When can mutations arise?
Spontaneously during DNA replication.
What is meant by spontaneous mutations?
Permanent changes in DNA that occur without any outside influence.
What is the typical natural mutation frequency?
1 or 2 in 100000 genes per generation.
What is the name given to something that can increase the number of mutations?
Mutagenic agents / mutagens.
List and describe possible mutagenic agents?
- High energy radiation: α particles, β particles, and short-wavelength radiation (like X-Rays and UV) can disrupt the structure of DNA.
- Chemicals: such as nitrogen dioxide that directly alters the structure of DNA or interferes with transcription. OR benzopyrene (a constituent of tobacco smoke) that inactivates the tumour suppressor gene TP53.
What are the costs and benefits of gene mutation?
- Benefit: produce genetic diversity necessary for natural selection and speciation.
- Cost: almost always harmful and produce an organism that is less well suited to its environment.
What is cell differentiation?
The process by which each cell develops into a specialised structure suited to the role that they will cay out.
If all (most) cells contain exactly the same genes, why are some cells better than others for specific tasks?
Only certain genes are expressed (turned on) in any one cell, at any one time.
What are ways in which genes are prevented from expressing themselves?
- Preventing transcription, and so preventing the production of mRNA.
- Preventing translation.
What are stem cells?
Cells that retain the ability to differentiate into other cells.
How are stem cells replaced?
They divide to form an identical copy of themselves in a process called self-renewal.
Where do stem cells originate in mammals?
Embryonic stem cells: from embryos in the early stages of development - can differentiate into any type of cell.
Umbilical cord blood stem cells: from umbilical cord blood - similar to adult stem cells.
Placental stem cells: found in the placenta - develop into specific types of cells.
Adult stem cells: found in body tissues of the fetus through to adult - spesific to a particular tissue or organ to maintain and repair throughout life.
How are different stem cells classified?
Totipotent stem cells:
- found in early embryos.
- can differentiate into any type of cell.
- example: zygote.
Pluripotent stem cells:
- found in embryos.
- can differentiate into most types of cell.
- example: embryonic stem cells and fetal stem cells.
Multipotent stem cells:
- found in adults.
- can differentiate into multiple specialised cells.
- example: adult stem cells and umbilical cord blood stem cells
Unipotent stem cells:
- made in adult tissue.
- can differentiate into only one type of cell.
- example: skin cells.
What are iPS cells and how are they made?
Induced pluripotent stem cells.
- Unipotent cells are taken from a donor.
- In a lab genes are induced and transcriptional factors are addaed.
- This is done to turn on genes that were turned off.
- This makes them similar to embryonic stem cells but they are capable of self-renewal.
How can pluripotent cells be used in treating human disorders?
- They can be used to regrow tissue that has been damaged (either accidentally or by disease).
Examples (do not need to know):
- Heart muscle cells: can treat heart damage like from heart attacks.
- Skeletal muscle cells: can treat muscular dystrophy.
- β cells (of the pancreas): can treat type 1 diabetes.
- Nerve cells: can treat Parkinson’s, multiple sclerosis, strokes, Alzheimer’s, paralysis due to spinal injury.
- Blood cells: Leukaemia and inherited blood diseases.
- Skin cells: Burns and wounds.
- Bone cells: Osteoporosis.
- Cartilage cells: Osteoarthritis.
- Retina cells (of the eye): Muscular degeneration.
What are the general principals involved in controlling the expression of a gene by controlling transcription?
- The gene is switched on by specific molecules that move from the cytoplasm into the nucleus (transcription factors)
- Each transcription factor has a site that binds to a specific base sequence of DNA in the nucleus.
- When it binds, causes the region of DNA to begin transcription.
- mRNA is produced and its information is translated into polypeptides.
- When a gene is not being expressed, the site of the transcription factor that binds to DNA is not active.
- As the site of the transcriptional factor binding to DNA is inactive it cannot cause transcription and polypeptide synthesis.
How can a hormone start transcription?
- By combining with receptors on the transcriptional factor.
Describe the process in which oestrogen stimulates transcription?
- Lipid soluble oestrogen diffuses easily through the phospholipid part of the cell-surface membrane.
- Inside the cytoplasm, it binds to the complementary site of a receptor molecule of the transcriptional factor.
- This changes the shape of the DNA binding site on the transcriptional factor, which can now bind to DNA (is activated).
- It can also now enter the nucleus via nuclear potes and bind to its specific base sequence on DNA.
- This stimulates transcription of the gene that makes up the portion of DNA.
What is epigenetics?
Heritable changes in gene function without changing the sequence of DNA.
What are tags?
chemicals that cover DNA and histones.
What is the epigenome?
All the chemical tags a call has received in its lifetime.
What effect does the epigenome have on the DNA-histone complex?
It determines the shape of the DNA-histone complex leading to epigenetic silencing or transcription.
Why is the epigenome flexible as opposed to the fixed genetic code?
- The chemical tags respond to the environment whilst the genome remains constant (apart from during random mutations which are rare).
- This environmental change may be due to factors like stress or diet.
How does an environmental signal affect the epigenome?
- Environmental signals stimulate proteins to carry its message inside the cell.
- It is passed by a series of other proteins into the nucleus.
- the message is passed to a specific protein which attaches to a specific sequence of bases.
- It either changes acetylation of histones leading to the activation or inhibition of a gene - methylation of DNA by attracting enzymes that can add or remove methyl groups.
What does it mean when a gene is switched on?
- Where the association of histones with DNA is weak, the DNA-histone complex is less condensed.
- This makes the DNA accessible by transcription factors.
- This initiates the production of mRNA so the gene is switched on.
What does it mean when a gene is switched off?
- Where the association of histones with DNA is strong, the DNA-histone complex is more condensed.
- This makes the DNA not accessible by transcription factors.
- This cannot initiate the production of mRNA so the gene is switched off.
What is acetylation?
The process whereby an acetyl group is transferred to a molecule.
Describe what happens during hypoacetylation (decreased acetylation)?
- The positive charges on histones increases, which increases their attraction to the phosphate group to DNA.
- This makes the association between DNA and histones stronger, so the DNA-histone complex is more condensed.
- Transcription factors are unable to access the DNA.
- mRNA production isn’t initiated from DNA.
- So the gene has been switched off.
What is methylation?
The addition of a methyl group (CH₃) to a molecule (in this case the cytosine base of DNA.