1
Q
What is a mutation?
A
A MUTATION is a random change to the genetic material.
A mutation changes the DNA, involving difference to the structure of number of chromosomes. Mutations occur spontaneously during DNA replication before cell division.
2
Q
What may cause a mutataion?
A
Certain chemicals, such as tar in tobacco smoke, and ionising radiation such as UV lights X-rays and gamma rays, may be mutagenic.
3
Q
What are the different types of genetic mutation?
A
- Point mutations (one base pair substitutes another), which include, silent, missense and nonsense mutations.
- Indel mutations (one+ nucleotides inserted or deleted causing a frame shift) which include an insertion and a deletion muation.
4
Q
The structure of a DNA molecule makes it stable and fairly resistant to corruption of the genetic information stored within it. But when may any errors occur?
A
Errors may occur during replication of a DNA molecule:
- Mutations during mitotic division are somatic mutations so are not inherited by offspring - yet they can cause cancerous tumours to develop
- Mutations during meiotic division are gamete mutations so are inherited by offspring.
5
Q
What may a mutation effect?
A
A mutation may affect protein production and function.
6
Q
What is a silent mutation?
A
- A point mutation involving a change to the base triplet, where that triplet still codes for the same amino acid is a silent mutation.
7
Q
Why might a silent muatation occur?
A
- This can occur as every amino acid involved in protein synthesis, apart from methionine, have more than one base triplet code. This means there is not a change to the sequence of amino acids in a protein: known as the ‘redundancy’ or ‘degeneracy’ of the genetic code.
- This consequently means there is no change in the primary structure of the protein, and therefore the secondary and tertiary structures.
8
Q
What is a missense mutation?
A
- A point mutation involving a change to the base triplet sequence, where that triplet codes for a different amino acid is a missense mutation.
- This consequently means there is a change in the primary structure of the protein, and therefore the secondary and tertiary structures, altering its shape and preventing the protein from carrying out its usual function.
9
Q
Give an example of an disease resulting from a missense mutation.
A
An example of a disease resulting from a missense mutation is sickle cell anaemia. There is a mutation on the sixth base triplet of the gene for the β-polypeptide chains of haemoglobin: glutamic acid is substituted for valine. This results in deoxygenated haemoglobin crystallising within erythrocytes, causing them to become sickle shaped, blocking capillaries and depriving tissues of oxygen.
10
Q
Describe a nonsence mutation.
A
- A point mutation involving a change to the base triplet, where that triplet codes for a termination codon is a nonsense mutation.
- This consequently means a truncated protein is produced which will not function, so it will be degraded within the cell.
11
Q
Give an example of a disease caused by a nonsense muation.
A
An example of a disease resulting from a nonsense mutation is the genetic disease Duchenne muscular dystrophy.
12
Q
Describe an indel mutation.
A
- If nucleotide base pairs, not in multiple of three, are inserted in or deleted from the gene, all subsequent base triplets will be altered - this is called a frameshift. This is because the code is non-overlapping and read in groups of three bases.
- This consequently means there is a change in the primary structure of the protein, and therefore the secondary and tertiary structures, altering its shape and preventing the protein from carrying out its usual function.
13
Q
What may an indel mutation cause within the cell?
A
- If the protein is very abnormal, it will rapidly degrade within the cell.
- An example of a disease resulting from a deletion mutation are some forms of thalassaemia, a haemoglobin disorder.
14
Q
Why might a frameshift not be caused by an indel mutation?
A
Insertions or deletions of a triplet of base pairs result in the addition of loss of an amino acid, and not a frameshift.
15
Q
What is it called when a base triplet is repeated?
A
Expanding triple nucleotide repeates
16
Q
Describe an expanding triple nucleotide repeate.
A
In an expanding triple nucleotide repeat, the number of CAG triplets in the gene with the repeating triplet -CAG CAG CAG- can increase at meiosis from generation to generation. For example, Huntington disease genotype is caused by the number of the CAG triplet repeats rising above a critical number so that the individual will develop the symptoms later in life.
17
Q
Not all mutations are harmful, give an example of an mutation that could be benifical, or harmful.
A
- A mutation that is beneficial and non-beneficial is the mutation that gave rise to blue eyes 6000-8000:
- In temperature zones, it may enable people to see better in less bright light
- In areas of high sunlight intensity, the lack of iris pigmentation may lead to lens cataracts.
18
Q
Why might a mutation be beneficial?
A
Many mutations have helped to drive evolution through natural selection as different alleles of a particular gene are produced via mutation.
19
Q
Give two examples of benefical mutations.
A
- A mutation that is beneficial is the mutation that gave rise to black skin:
- Early humans in Africa would have high concentration of melanin protecting them from sunburn and skin cancer.
- Another mutation that is beneficial is the mutation that gave rise to light skin:
- When humans migrated to colder regions pale skin allowed vitamin D to be made with a lower intensity of sunlight.
20
Q
Give an example of a muation that is neutral.
A
Examples of mutation that are neutral are:
- Inability to smell certain flower, including freesias and honeysuckle
- Differently shaped ear lobes.
21
Q
How is energy and resources conserved by transcriptional gene regulation in prokaryotic cells?
A
- Enzymes that catalyse the metabolic reactions involved in basic cellular functions are synthesise at a fairly constant rate.
- However, enzymes that may only be needed under specific conditions are synthesised at varying rates, according to the cell’s needs.
- This conserves energy and resources.
22
Q
Where are the controll sites of the Lac Operon and their functions?
A
Promotor region (P)
Enzyme RNA polymerase binds to begin transcription of the structural genes
Operating region (lacO)
Repressor protein LacI binds to prevent RNA polymerase from binding to promoter region
23
Q
What are the structual genes od the Lac Operon and their function?
A
lacZ
Codes for β-galactosidase
lacY
Codes for lactose permease
24
Q
What is the regualatory gene, and its function on the lac operon?
A
I
Codes for repressor protein LacI
25
What is an example of the effect of the Lac Operon on an E.coli bacterial cell?
1. glucose is used as a respiratory substrate.
2. If glucose is absent and lactose is present, lactose induces the production of two enzymes:
3. _Lactose permease_: allows lactose to enter the bacterial cell
4. _-galactosidase_: hydrolyses lactose to glucose and galactose.
5. The presence of lactose induces the production of the enzyme, not the absence of glucose.
26
What is the lac Operon?
The lac operon is of a length of DNA, about 6000 base pairs long.
27
Describe how the lac Operon mechanism prevents constant transcription of the structural proteins.
1. The regulatory gene is expressed causing the production of protein repressor molecule LacI
2. This molecule binds to the operator preventing RNA polymerase from binding to the promoter region, stopping transcription of the structural genes
3. When lactose is added to the culture medium, once there is an absence of glucose, molecules of lactose induce conformational change to the LacI repressor molecules, preventing them from binding to the operator
28
How does the lac operon allow transcription of the structural proteins?
* cAMP activates CAP which binds to the CAP region to attract RNA polymerase to bind to the promoter region promoter which can then begin transcribing the structural genes into mRNA
* The mRNA will then be translated into the two enzymes.
29
Describe an investigation observing the effect of the lac operon.
1. If E. coli are grown in media without lactose then it is added with an unnatural substrate for β-galactosidase (ONPG), after a while, the lactose induces the enzymes to convert ONPG to a yellow product that can be easily seen.
2. If this is repeated using E. coli bacteria that have been grown in lactose, the yellow product of ONPG conversion appears much faster.
3. If it is carried out using E. coli grown in the absence of lactose and not given any lactose, ONPG is not converted and no yellow colour is seen.
30
What is cell differentiation in eukaryotic cells?
Every cell in a eukaryotic organism has the same genome but, because cells use it differently, they function differently: this is known as **cell differentiation**, yet the same basic 'housekeeping' genes will usually be expressed.
31
What are transcription factors?
Transcription factors are proteins, or short non-coding pieces of RNA, that act within the cell's nucleus to control gene expression.
32
What do transcription factors do?
* Slide along a part of the DNA molecule, seeking and binding to their specific promoter regions
* Aid or inhibit the attachment of RNA polymerase to the DNA, activate or suppressing transcription of the gene
* May regulate the cell cycle, like regulating tumour suppressor gene and proto-oncogenes to control cell division as mutations to these genes can lead to cancer
33
How much are transcription factors used in our DNA, and how do the promoter regions control the amount of DNA?
8% of genes in the human genome encode transcription factors and many genes have their promoter regions some distance away along the unwound length of the DNA but, because of how the DNA can bend, the promoter region may not be too far away so spatially.
34
What are non-coding and coding regions of DNA called?
* _INTRONS_: non-coding regions of DNA which are not expressed
* _EXONS_: coding regions of DNA which are expressed
35
Where is post-transcriptional gene regulation used?
All the DNA of a gene is transcribed, the introns and exons, giving a primary mRNA strand which is then edited as the RNA introns are spliced, using the **endonuclease enzyme**, so that the remaining RNA exons are joined together.
Genes can be spliced in different ways so a length of DNA which has introns and exons, according to how its spliced, may encode for more than one protein.
(NOTE: Introns may encode for proteins so they become short non-coding length of RNA involved in gene regulation. )
36
What are the three types of gene regulation?
1. transcriptional
2. Post-transcriptional
3. Post-translationional
37
Describe post-translational gene regualtion.
_Activation of proteins by cAMP_
Post-translational regulation of gene expression involves the activation of proteins by, for example, **phosphorylation**.
Cyclic adenosine monophosphate (cAMP) is a secondary messenger involved in activating enzymes, stimulating transcription, by phosphorylation.
38
Draw or note the process of activating a protein in post-translational gene regulation.
39
How is PKA activated in post-translational gene regulation?
1. A signalling molecule, such as the protein hormone glucagon, binds to a receptor on the plasma membrane of the target cell.This activates a transmembrane protein which activates a G protein.
2. The activated G protein activates adenyl cyclase enzymes.
3. Activated adenyl cyclase enzymes catalyse the formation of many molecules of cAMP from ATP.
4. cAMP activates protein kinase A (PKA)
40
How does the activation of PKA cause post-translational gene regulation?
6. PKA creates a phosphorylation cascade, hydrolysing ATP in the process, of protein
7. The cascade reaches a cAMP response element-binding (CREB) protein to activate it.
8. The protein enters the nucleus and acts as a transcription factor to regulation transcription.
41
What are homeobox sequences?
HOMEOBOX SEQUENCES are a sequence of 180 base pairs (excluding introns) found within genes that are involved in regulating patterns of anatomical development in animals, fungi and plants.
42
What is the purpose of homeotic genes?
The homeotic genes are a large and ancient family of genes involved in controlling the anatomical development (**morphogenesis**) of an organism so that all the structures develop in the correct location according to the body plan - several of these genes contain **homeobox sequences**.
43
Describe a homeodomain and its
1. Each homeobox sequence is a stretch of 180 DNA base pairs (excluding introns) encoding a 60-amino acid sequence, called a **homeodomain**, within a protein.
2. The homeodomain sequence can fold into a particular shape and bind to DNA to regulate the transcription of adjacent genes so these proteins are transcription factors and act within the cell nucleus.
3. The shape that these homeodomain-containing proteins fold into is called H-T-H as it consists of two α-helices (H) connected by one turn (T).
4. Part of the homeodomain amino acid sequence recognises the TAAT sequence of the enhancer region (a region that initiates or enhances transcription) of a gene to be transcribed.
44
_Similarity and conservation of homeobox gene sequences;_
Explain the discovery of homeobox genes.
* The homeobox gene sequence was first identified in 1983 within the homeotic genes of the fruit fly, Drosophila melanogaster. In 1984, scientists led by Walter J. McGinnis discovered a very similar base homeobox gene sequence in a mouse. This informed scientists that these gene these gene sequences are crucial for the regulation of development and differentiation in organisms.
* Also in 1984, Edward de Robertis discovered a subset of homeobox genes, **Hox genes**, in the African clawed frog, Xenopus.
45
What did the discovery of hox genes lead to?
* This discovery led to a new branch of biology called evolutionary development or 'evo-devo'.
1. Homeobox genes are found in animals, plants and fungi
2. Hox genes are only found in animals.
46
What does the history of homeobox sequences tell us?
* Molecular evidence indicates that homeobox genes are present in Cnidaria so these genes arose before the Palaeozoic era which began 541 million years go, and before bilaterally symmetrical organisms evolved
* This indicates that these genes first arose in an early ancestor, which gave rise to each of these types of organisms, and have been **conserved**. The similarity between all organisms studied to date extends across wide evolutionary distances.
47
What are Hox genes?
* HOX GENES are a subset of homeobox genes, found only in animals; involved in the formation of anatomical features in correct locations of body plane.
48
What do Hox genes regulate?
The *Hox* genes regulate the development of embryos along the anterior-posterior (head-tail) axis by controlling which body parts grow where.
49
What is caused by the Hox genes misfunctioning?
If Hox genes are mutated, abnormalities can occur such as the antennae on the head of Drosophila developing legs, or mammalian eyes developing on limbs.
50
Why have hox clusters formed?
At some stage during evolution, the Hox clusters have been duplicated: Hox genes are arranged into clusters and each cluster may contain up to 10 genes. In tetrapods (four-limbed vertebrates), for example, there are four clusters.
51
Describe collinearity.
In early embryonic development, *Hox* genes are active and are expressed in order along the anterior-posterior axis of the developing embryo. The sequential and temporal (in time) order of the gene expressions corresponds to the sequential and temporal development of the various body parts, a phenomenon known as **collinearity**.
52
How do Hox genes create the desired function?
* Hox* genes encode homeodomain proteins that act in the nucleus as transcription factors and can switch on cascades of activation of other genes that promote mitotic cell division, apoptosis, cell migration and also help to regulate the cell cycle.
* Hox* genes are similar across different classes of animals; a fly can function properly with a chicken *Hox* gene inserted in place of its own.
53
What substance helps regulate Hox gene activity?
In humans, retinoic acid helps regulate the activity of *Hox* genes. Vitamin A (retinol), found in the liver, is a potent source of retinoic acid, but too much eaten during pregnancy can cause foetal abnormalities. It is also toxic to adults in large quantities.
54
How are Hox genes regulated?
Hox genes are regulated by other genes called **gap genes** and **pair-rule genes**, in turn, these genes are regulated by materially supplied mRNA from the egg cytoplasm.
55
How are homeobox genes involved in mitosis?
Mitosis is regulated by homeobox and *Hox* genes to ensure that each new daughter cell contains the full genome and is a clone of the parent cell.
56
Mitosis, how is the cell type controlled?
During cell differentiation some of the genes in a particular type of cell are 'switched off' and are not expressed.
57
What constant was disocvered in the 20th century, involving mitosis?
In 1962, Leonard Hayflick showed that normal body cells divide a limited number of times, around 50 - known as the **Hayflick constant**, before dying.
58
What is apoptosis?
**Apoptosis** is programmed cell death.
59
When was apoptosis discovered, and by who?
1. In 1965, John Foxton Ross Kerr re-examined and researched the idea of programmed cell death, first described in 1842 by Carl Vogt.
2. In 1972, the term 'apoptosis' was used for programmed cell death.
60
What is the unporgammed death of cells?
**Necrosis** is the death of cells due to trauma which involved hydrolytic enzymes, unlike apoptosis.
61
What are the stages of apoptosis?
_The stages of apoptosis, which is a **quick process**, are as follows:_
1. Enzymes break down the cell cytoskeleton
2. The cytoplasm becomes dense with tightly packed organelles
3. The cell surface membrane changes and small protrusions called **blebs** form
4. Pyknosis occurs which is the condensing of the chromatin
5. Karyorrhexis occurs which is the fragmentation of the DNA after the nuclear envelope breaks
6. The cells breaks into vesicles
7. The debris is ingested by phagocytic cells so that the cell debris does not damage any other cells or tissues.
62
How is apoptosis controlled?
* Apoptosis is controlled by cell signals which are release in response to internal and external cell stimuli.
* These molecules include cytokines from the immune system, hormones, growth factors, nitric oxide and stress.
63
What induces apoptosis?
Nitric oxide can induce apoptosis by making the inner mitochondrial membrane more permeable to hydrogen ions and dissipating the proton gradient. Proteins are released into the cytoplasm where they bind to apoptosis inhibit proteins, allowing apoptosis to occur.
64
Why is apoptosis an integral part of plant and animal tissue development?
1. Prevents extensive proliferation of cell types is prevented by pruning through apoptosis, without the release of hydrolytic enzymes that could damage surrounding tissues.
2. Causes digits to separate from each other during limb development
3. Removes ineffective or harmful T-lymphocytes during the development of the immune system.
65
What is the rate of apoptosis?
In children aged between 8 and 14 year, 20 – 30 billion cells per day apoptose; in adults, 50 – 70 million cells per day apoptose.
66
Why is the regualtion of apoptosis important?
The rate of cells dying should equal the rate of the cells produced by mitosis, where cell signalling plays a crucial role in maintaining the right balance:
* Not enough apoptosis leads to the formation of tumours
* Too much apoptosis leads to cell loss and degeneration.
Biology A2 OCR
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