1
Q
What is a mutation?
A
- Any change to the quantity or the structure of DNA of an organism.
- A gene mutation is a change or rearrangement of nucleotide bases.
2
Q
What is substitution of bases?
A
A nucleotide in a section of DNA molecule is replaced by another nucleotide with a different base.
3
Q
What is the consequence of mutations? - stop codons
A
- The formation of one of the three stop codons that mark the end of a polypeptide chain.
- The production of the polypeptide chain would stop prematurely.
- The final protein would be significantly different and the protein not perform its normal function.
4
Q
What is the consequence of mutations? - different
A
- The formation of a codon for a different amino acid, so the polypeptide would differ by a single amino acid.
- The protein may differ in shape and not function properly.
- For an enzyme, the active site may no longer fit the substrate and so not catalyse the reaction.
- Example is the mutation that causes sickle cell anaemia.
5
Q
What is the consequence of mutations? - same
A
- The formation of a different codon but one that produces the same amino acid as before.
- This is due to the degenerate nature of the genetic code.
- The mutation has no effect on the protein.
6
Q
What is deletion of bases?
A
- The loss of a nucleotide base from a DNA sequence.
- This creates a frame shift, and so the gene is read in the wrong three-base groups.
- Most triplets and hence amino acids will be different.
- It will lead to a non-functional protein that could considerably alter the phenotype.
- A deleted base at the end of the chain will have a smaller effect but still have consequences.
7
Q
What is addition of bases?
A
- An extra base is inserted in the sequence.
- This causes a frame shift, unless 3 bases are added, or any multiple of 3.
- The resulting polypeptide will be different, but not to the same extent as if there was a frame shift.
8
Q
What is duplication of bases?
A
- One or more bases are repeated.
- This produces a frame shift.
9
Q
What is inversion of bases?
A
- A group of bases become separated from the DNA sequence and re-join at the same position but in the inverse order.
- This effects the amino acid sequence that results.
10
Q
What is translocation of bases?
A
- A group of bases becomes separate from the DNA sequence on one chromosome and become inserted into the DNA sequence on another chromosome.
- They often have significant effects and lead to an abnormal phenotype.
- This includes developing some cancers and reduced fertility.
11
Q
Which mutations are most likely to have a significant impact and why?
A
Insertion, deletion, duplication, translocation. Because they produce a frameshift, meaning the entire amino acid sequence produced will be different
12
Q
Which mutations are most likely to have a smaller impact and why?
A
Substitution and inversion. Because they only alter one or very few triplets, the amino acid sequence might not be affected due to the degenerate nature of the genetic code.
13
Q
Is a mutation resulting in a change to the amino acid sequence always harmful?
A
No; may be neutral if the resulting change in protein has no effect on the organism. Also may be beneficial, which is the basis for evolution and natural selection
14
Q
What are the causes of mutations?
A
- Mutations occur with predictable frequency, around 1 or 2 mutations per 100,000 genes per generation.
- This rate can be increased by mutagenic agents - radiation and chemicals.
15
Q
How does radiation increase mutations?
A
- High energy ionising radiation for example alpha and beta particles, and short wavelength radiation like X-rays and UV light.
- These disrupt the structure of DNA.
16
Q
How do chemicals increase mutations?
A
- chemicals such as nitrogen dioxide may alter the structure of DNA or interfere with transcription.
- Benzopyrene, a constituent of tobacco smoke, is a powerful mutagen that inactivates a tumour-suppressor gene TP53, leading to cancer.
17
Q
What are the costs and benefits of mutations?
A
- They produce the genetic diversity necessary for natural selection and speciation.
- But they are almost always harmful and produce an organism less well suited to its environment.
- They occur in body cells rather than gametes, leading to the disruption of normal cellular activities - cell division e.g. cancer.
18
Q
Why are cells differentiated?
A
Cells cannot be totally efficient at all functions, because they each require different cellular structure, enzymes and other proteins.
19
Q
What are the origins of cells?
A
- All the cells are derived by mitotic division of the zygote.
- So they all contain the exact same genes, and so capable of making everything the body can produce.
- But, only certain genes are expressed in any one cell at any one time.
20
Q
How does gene expression vary?
A
- Some genes are permanently expressed in all cells, e.g. the genes that code for enzymes involved in respiration, transcription, translation, membrane synthesis, ribosome and tRNA synthesis.
- Other genes are expressed when they are needed.
21
Q
What are differentiated cells?
A
- They each produce different proteins.
- The proteins a cell produces are coded for by the genes that are expressed.
22
Q
What are totipotent cells?
A
- Cells e.g. fertilised eggs, which can mature into any body cell.
- The early cells derived from the fertilised egg are also totipotent.
23
Q
How is gene expression prevented?
A
- It would be wasteful to produce proteins not needed for the specialised cells.
- So to conserve energy and resources, a variety of stimuli ensure these genes are not expressed.
By: - preventing transcription and so preventing the production of mRNA,
- preventing translation.
24
Q
Can specialised cells develop into other cells?
A
- Xylem vessels, which transport water and red blood cells, are so specialised that they lose their nuclei once mature.
- As the nucleus contains the genes, these cells cannot develop into other cells.
- Only stem cells can differentiate into other cells.
25
What are stem cells?
- Undifferentiated dividing cells in adult animal tissues that need to be constantly replaced.
- So they have the ability to divide to form an identical copy of themselves by self-renewal.
26
What are the 4 types of stem cells?
1. Totipotent = can develop into any cell type including the placenta and embryo
2. Pluripotent = can develop into any cell type excluding the placenta and embryo
3. Multipotent - can only develop into a few different types of cell
4. Unipotent - can only differentiate into a single type of cell
27
Where do stem cells originate from?
- Embryos in the early stages of development, can develop into any cell in the initial stages of development.
- Umbilical cord blood stem cells are similar to adult stem cells.
- Placenta stem cells develop into specific types of cells.
- Adult stem cells are found in the body tissues of the foetus through to the adult. They are specific to particular tissue or organ and produce the cells to maintain and repair tissues throughout it’s life.
28
What happens to totipotent cells during embryonic development?
Certain parts of the DNA are selectively translated so that only some genes are 'switched on', in order to differentiate the cell into a specific type and form the tissue that makes up the foetus
29
Give a unique feature of pluripotent cells and the use of this feature.
They can divide in unlimited numbers, and can therefore be used to repair or replace damaged tissue
30
What is a unipotent cell? Give an example
A cell that can only develop one type of cell. This happens at the end of specialisation when the cell can only propagate its own type. An example is cardiomyocytes (heart cells)
31
What type of stem cells are found in embryos?
- Totipotent and pluripotent
- Multipotent and unipotent cells are only found in mature mammals
32
What are some uses of stem cells?
- Medical therapies e.g. bone marrow transplants, treating blood disorders
- Drug testing on artificially grown tissues
- Research e.g. on formation of organs and embryos
33
How are induced pluripotent stem cells produced?
- From mature, fully specialised cells. The cell regains capacity to differentiate through the use of proteins, in particular transcription factors
34
What are induced pluripotent stem cells?
- iPS cells are a type of pluripotent cell produced from unipotent stem cells.
- The body cell is genetically altered in a lab to make them acquire the characteristics of embryonic stem cells.
35
How are iPS cells made?
- To make the unipotent cells acquire the new characteristics involves inducing genes and transcriptional factors within the cell to express themselves.
- This shows that adult cells retain the same genetic information that was present in the embryo, because the genes are capable of reactivation.
36
How are iPS cells different from embryonic?
- They are capable of self renewal - meaning they can potentially divide indefinitely to provide a limitless supply
- They could replace embryonic stem cells in medical research and treatment and so overcome many of the ethical issues surrounding the use of embryos
37
What are the uses of pluripotent cells?
- the cells can be used to regrow tissues that have been damaged in some way, either by accident or as a result of disease
38
What are the potential uses of human cells produced from stem cells?
Heart muscle cells - could treat heart damage, as a result of a heart attack
skeletal muscle cells - muscular dystrophy
ß cells of the pancreas - type 1 diabetes
nerve cells - Parkinson's disease, strokes, Alzheimer's disease
Blood cells - leukaemia, inherited blood diseases
skin cells - burns and wounds
bone and cartilage cells - osteoporosis
Retina cells of the eye - macular degeneration
39
What is a transcription factor?
a protein that controls the transcription of genes so that only certain parts of the DNA are expressed, e.g. in order to allow a cell to specialise
40
How do transcription factors work?
1. Move from the cytoplasm into nucleus
2. Bind to promoter region upstream of target gene
3. Makes it easier or more difficult for RNA polymerase to bind to gene. This increases or decreases rate of transcription
41
What hormone affects transcription and how does it work?
1. Steroid hormone oestrogen diffuses through the phospholipid of the cell membrane
2. Oestrogen binds with a site on a receptor molecule of the transcription factor, the site and shape complement each other
3. By binding with the site, the oestrogen changes shape of the DNA binding site on the transcription factor, which can now bind to DNA
4. the transcription factor can now enter the nucleus through a nuclear pore and bind to specific base sequences of DNA
5. The combination of the transcription factor with DNA stimulates transcription of the gene that makes up the portion of DNA
42
What is epigentics?
a heritable change in gene function without change to the base sequence of DNA
43
What is an epigenome?
- determines the shape of DNA-histone complex
- it keeps genes that are inactive in a tightly packed arrangement and therefore ensures that they cannot be read - epigenetic silencing. By contrast, it unwarps active genes so that DNA is exposed and can easily be transcribes (switches them on)
- DNA code is fixed, epigenome is flexible, the chemical tags respond to environmental changes
44
How has the epigenome changed in its lifetime?
- the epigenome of a cell is the accumulation of the signals it has received in its lifetime and therefore it acts like a cellular memory
- In early development, the signals come from within the cells of the foetus and the nutrition provided by the mother is important in shaping the epigenome
- After birth and throughout life - environmental factors affect the epigenome, although signals from within the body also influence it - these factors cause the epigenome to activate or inhibit specific sets of genes
45
How does the environment affect the epigenome?
The environmental signal stimulates proteins to carry its message inside the cell from where it is passed by a series of other proteins into the nucleus. Here the message passes to a specific protein which can be attached to a specific sequence of bases on the DNA
46
What affect does the protein bound to DNA have?
It can change:
- 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
47
What is the DNA-histone complex?
- where the association with histones is weak, the DNA-histone complex is less condensed - DNA is accessible by transcription factors which can initiate production of mRNA, the gene is switched on
- where the association is stronger, the DNA-histone complex is more condensed - DNA is not accessible by transcription factors, which therefore cannot initiate production of mRNA, the gene is switched off
48
What does condensation of the DNA-histone complex do?
- inhibits transcription
- it can be brought about by decreased acetylation of the histones or by methylation of DNA
49
What is acetylation?
the process whereby an acetyl group is transferred to a molecule - the group donating the acetyl group is acetylcoenzyme A
50
What is decreases acetylation?
it increases the positive charges on histones and therefore increases their attraction to the phosphate groups of DNA. The association between DNA and histones is stronger and the DNA is not accessible to transcription factors - they can't initiate mRNA production from DNA so the gene is switched off
51
How does increased methylation of DNA affect gene transcription?
- Involves addition of a CH3 group to cytosine bases which are next to guanine
- Prevents transcription factors from binding
- Therefore gene transcription is suppressed
52
How does decreased acetylation of DNA affect gene transcription?
- Positively charged histones are positively charged bind to negatively charged DNA
- Decreasing acetylation increases positive charge of histones
- Binding becomes too tight and prevents transcription factors from accessing the DNA. Therefore gene transcription is suppresses
53
How might epigenetics changes affect humans?
They can cause disease, either by over activating a gene's function or by suppressing it
54
Give an application of epigenetics
Treatments of various diseases
Development of ways to reverse epigenetic changes
55
How is epigenetics inherited?
It is thought that in sperm and eggs during the earliest stages of development a specialised cellular mechanism searches the genome and erases its epigenetic tags in order to return the cells to a genetic 'clean slate'. However, a few epigenetic tags escape this process and pass unchanged from parent to offspring
56
What is an example of epigenetic inheritance in humans?
When a mother has a condition known as gestational diabetes, the foetus is exposed to high concentrations of glucose. These high glucose concentrations cause epigenetic changes in the daughter's DNA, increasing the likelihood that she will develop gestational diabetes herself
57
How do epigenetics cause diseases?
- Altering any of the epigenetic processes can cause abnormal activation or silencing of genes
Such alterations have been associated with a number of diseases including cancer
58
How is methylation linked to cancer?
- there are specific sections of DNA that have no methylation in normal cells. However, in cancer cells these regions become highly methylated causing genes that should be active to switch off
- Epigenetics don't alter the sequence of DNA but they can increase the incidence of mutations. Some active genes normally help repair DNA so prevent cancers. In some people with various types of inherited cancer, it is found that increased methylation of these genes has led to these protective genes being switched off - damaged base sequence in DNA not repaired, cancer
59
How can disease be treated with epigenetics?
- They use drugs to inhibit certain enzymes involved in either histone acetylation or DNA methylation
- Diagnostic tests - help to detect the early stages of diseases such as cancer, brain disorders and arthritis. They can identify the level of DNA methylation and histone acetylation at an early stage of disease, allowing those with these diseases to seek early treatment and so have better chance of cure
60
What is the process of RNA interference, including the organisms in which it occurs?
RNA molecules act to inhibit gene expression, usually by destroying mRNA so that it cannot be translated. Occurs in eukaryotes and some prokaryotes
61
What is siRNA?
- Small Interfering RNA
- Acts as another mechanism to prevent a protein being formed from a gene by breaking down mRNA before translation.
62
What affect does siRNA have on gene expression?
- siRNA is a short double-stranded RNA molecule, about 20 base pairs long. It is made by special genes that are transcribed as normal to make single stranded RNA, which then folds back on itself by complementary base pairing to make a hairpin-like double stranded molecule
- In the cytoplasm siRNA binds to a protein called the RNA-induced silencing complex(RISC)
- RISC breaks the double-stranded siRNA into its separate strands. One strand remains attached to the RISC protein, while the other strand is discarded
- The RISC-RNA complex now binds to mRNA molecules in the cytoplasm by complementary base pairing. Any mRNA molecules with a base sequence complementary to the 20-base siRNA sequence will bind
- This binding causes RISC to cut the mRNA molecules in 2
- This cleaved mRNA can no longer be used in translation and is broken down by nuclease enzymes
63
What is cancer?
- a group of diseases caused by damage to the genes that regulate mitosis and the cell cycle. - leads to unrestrained growth of cells
- common and destructive disease
64
What are the 2 types of tumours?
Malignant - cancerous
Benign - non-cancerous
65
What are the characteristics of benign tumours?
- grow to a large size
- slow growth
- the cell nucleus has a relatively normal appearance
- cells are often well differentiated
- cells produce adhesion molecules that make them stick together and so they remain within the tissue from which they arise
- tumours are surrounded by a capsule of dense tissue and so remain as a compact structure
- Much less likely to be life-threatening but can disrupt functioning of a vital organ
- tend to have localised effects on the body
- can usually be removed by surgery-easy to treat
- rarely reoccur after treatment
- don't spread easily
66
What are the characteristics of malignant tumours?
- can grow to a large size
- grow rapidly
- the cell nucleus is often larger and appears darker due to an abundance of DNA
- cells become de-differentiated
- cells do not produce adhesion molecules and so they tend to spread to other regions of the body
- tumours are not surrounded by a capsule and so can grow finger-like projections into the surrounding tissue
- more likely to be life-threatening, as abnormal tumour tissue replaces normal tissue
- often have systemic effects such as weight loss, fatigue
- removal usually involves radiotherapy and/or chemotherapy as well as surgery
- More frequently reoccur after treatment
67
What are oncogenes?
- mutations of proto-oncogenes
68
What is the role of proto-oncogenes?
- stimulate a cell to divide when growth factors attach to a protein receptor on its cell-surface membrane, activating the genes that cause DNA to replicate and the cell to divide
- Control cell division - in particular, code for proteins that stimulate cell division
69
How are proto-oncogenes involved in developing cancer?
- Mutation in the gene could turn it into a permanently activated oncogene. Decreased methylation or increased acetylation can cause excess transcription
- this results in uncontrolled cell division and formation of a tumour
70
What is the role of the tumour-suppressor genes?
- code for proteins that control cell division; in particular, stopping the cell cycle when damage is detected. They are also involved in programming apoptosis i.e. 'self destruction' of the cell
71
How can tumour suppressor genes be involved in developing cancer?
- a mutation in the gene could code for a non-functional protein. Increased methylation or decreased acetylation could prevent transcription
- cells will divide uncontrollably resulting in a tumour
72
How does abnormal methylation of genes cause cancer?
Hyper-methylation of tumour-suppressor genes or oncogenes can impair their function and cause the cell to divide uncontrollably
73
How can hypermethylation lead to cancer?
- it occurs in the promoter region, leading to the tumour suppressor gene being inactivated
- so, transcription of the promoter regions of tumour suppressor genes is inhibited
- the tumour suppressor gene is therefore silenced(switched off)
- as the tumour suppressor gene normally slows the rate of cell division, its inactivation leads to increased cell division and the formation of a tumour
74
How can oestrogen be involved un developing breast cancer?
- because its an activator of RNA polymerase, it means that in areas of high oestrogen concentrations, such as adipose tissue in the breasts, cell division can become uncontrolled
75
What is the difference between oncogenes and tumour suppressor genes?
while oncogenes cause cancer as a result of the activation of proto-oncogenes, tumour suppressor genes cause cancer when they are inactivated
76
How does oestrogen cause a tumour?
- the mechanism by which oestrogen effectively activates a gene by releasing an inhibitor molecule that prevents transcription
- if the gene that oestrogen acts on is one that controls cell division and growth, then it will be activated and its continued division could produce a tumour
77
What is the genome?
the complete set of genetic information contained in the cells of an organim
78
What is genome sequencing?
identifying the DNA base sequence of an individual. This allows us to determine the amino acid sequence of the polypeptides coded for by that DNA
79
What is the proteome?
the complete set of proteins that can be produced by a cell
80
Can we directly translate the genome into the proteome?
in simple organism, yes. In complex organisms, due to the presence of non-coding DNA and regulatory genes, it is much harder to obtain the proteome
81
Give an application of sequencing the proteome in simple organisms.
Identifying potential antigens for use in vaccine production
82
Give some applications of genome sequencing.
- comparing genomes between species to determine evolutionary relationships
- genetic matching
- personalised medicine
- synthetic biology
83
How have sequencing methods changed over time?
Used to be a manual process, however now it has become automated. A reaction mixture is created and after the process is complete, a machine reads the base sequence, more cost effective
Biology A2
flashcards
Decks in class (19)
# Cards
-
Energy transfers in and between organisms0
-
5.1 Photosynthesis82
-
5.2 Respiration63
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5.3 Energy and Ecosystems33
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5.4 Nutrient Cycles33
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Organisms respond to changes in their internal and external environments0
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6.1 Internal and external stimuli71
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6.2 Nervous coordination55
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6.3 Skeletal muscles34
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6.4 Homeostasis82
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Genetics, populations, evolution and ecosystems0
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7.1 Inheritance42
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7.2 Populations8
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7.3 Evolution may lead to speciation27
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7.4 Populations in ecosystems43
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The control of gene expression0
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Gene expression83
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Gene technologies53
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Gene technologies part 241
