Topic 8: The Control Of Gene Expression

Question 1

Define gene mutation

Answer 1

Changes in the DNA base sequence which can arise spontaneously during DNA replication

Question 2

Define mutagenic agent

Answer 2

Factor that increases rate of mutation

Question 3

Examples of mutagenic agent

Answer 3

UV light
Alpha particles

Question 4

Explain how a gene mutation can lead to the production of a non-functional protein / enzyme

Answer 4

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

Question 5

What are the 6 types of mutations?

Answer 5

1) Substitution
2) Addition
3) Deletion
4) Duplication
5) Inversion
6) Translocation

Question 6

Describe substitution

Answer 6

A base is replaced by a different base in DNA

Question 7

Describe addition

Answer 7

1 or more bases are added to the DNA base sequence

Question 8

Describe deletion

Answer 8

1 or more bases are lost from the DNA base sequence

Question 9

Describe duplication

Answer 9

A sequence of DNA bases are repeated / copied

Question 10

Describe inversion

Answer 10

Sequence of bases detached from the DNA sequence & rejoins at the same position in inverse order

Question 11

Describe translocation

Answer 11

Sequence of DNA bases detaches and is inserted at a different location within the same (or different) chromosome

Question 12

Why don’t all gene mutations affect the order of amino acids?

Answer 12

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

Question 13

Define degenerate

Answer 13

1 amino acid can be coded for by more than 1 triplet

Question 14

Why aren’t changes in amino acid sequence always harmful?

Answer 14

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

Question 15

Explain frame shift

Answer 15

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

Question 16

What happens if a multiple of 3 bases is added / removed?

Answer 16

No frame shift but will result in an extra / less amino acid in the encoded polypeptide

Question 17

How can frame shift lead to a shorter polypeptide?

Answer 17

Produce a stop codon

Question 18

Define a stem cell

Answer 18

Undifferentiated / unspecialised cell which can divide by mitosis and differentiate into other types of cells

Question 19

How do stem cells become specialise during development?

Answer 19

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

Question 20

Describe totipotent cells

Answer 20

1) Occur for limited time in early mammalian embryos

2) Can divide and differentiate into any type of body cell

Question 21

Describe pluripotent cells

Answer 21

1) Found in mammalian embryos
2) Can divide and differentiate into most cell types

Question 22

What is the only cell type in the body that isn’t pluripotent?

Answer 22

Placenta cells

Question 23

Describe multipotent cells

Answer 23

1) Found in mature mammals
2) Can divide and differentiate into a limited number of cell types

Question 24

Example of multipotent cells

Answer 24

Bone marrow

—> can divide and differentiate into different types of blood cells

Question 25

Describe unipotent cells

Answer 25

1) Found in mature mammals 2) Can divide into just one type of cell

Question 26

Example of unipotent cells

Answer 26

Unipotent cells in the heart can divide and differentiate into cardiomyocytes

Question 27

How can stem cells be used to treat human disorders?

Answer 27

1) Transplanted into patients to divide in unlimited number 2) Then differentiate into required healthy cells

Question 28

Examples of stem cells using in treatment of human disorders

Answer 28

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

Question 29

What does iPS cells stand for?

Answer 29

Induced pluripotent stem cells

Question 30

How are iPS cells produced?

Answer 30

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

Question 31

What happens once iPS cells are produced?

Answer 31

They can divide and differentiate into healthy cells to transplant into the same patient

Question 32

What is the pathway for iPS cell production?

Answer 32

1) Somatic cells from patient + transcription factors —> iPS cells 2) iPS cells differentiate into specialised cells 3) Specialised cells are transplanted into patient

Question 33

Positives for using stem cells in treating human disorders

Answer 33

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

Question 34

Negatives for using stem cells in treating human disorders

Answer 34

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

Question 35

Describe transcription factors?

Answer 35

Proteins which regulate transcription of specific target genes in eukaryotes by binding to a specific DNA base sequence on a promoter region

Question 36

Describe how transcription can be regulated using transcription factors

Answer 36

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

Question 37

How does oestrogen affect transcription?

Answer 37

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

Question 38

Why does oestrogen only affect target cells?

Answer 38

Other cells don’t have oestrogen receptors

Question 39

Define epigenetics

Answer 39

Heritable changes in gene function without changes to base sequence of DNA, caused by changes in the environment

Question 40

Define epigenome

Answer 40

All chemical modification of DNA and histone proteins —> methyl groups in DNA and acetyl groups on histones

Question 41

What happens to the methylation of DNA if transcription is inhibited?

Answer 41

Increases

Question 42

What happens to methylation of DNA if transcription is allowed?

Answer 42

Decreases

Question 43

What happens to acetylation of histones when transcription is inhibited?

Answer 43

Decreases

Question 44

What happens to acetylation of histones if transcription is allowed?

Answer 44

Increases

Question 45

How does methylation inhibit transcription?

Answer 45

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

Question 46

How does acetylation inhibit transcription?

Answer 46

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

Question 47

Relevance of epigenetics on disease development and treatment

Answer 47

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

Question 48

What is RNA interference?

Answer 48

Inhibition of mRNA produced from target genes, by RNA molecules --> inhibits depression of target gene

Question 49

Where does RNA interference occur?

Answer 49

Eukaryotes and some prokaryotes

Question 50

Describe the regulation of translation of RNA interference

Answer 50

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

Question 51

How do tumours and cancers form?

Answer 51

1) Mutations in DNA controlling mitosis can lead to uncontrolled cell division 2) Tumour is formed if this results in mass of abnormal cells

Question 52

What are the types of tumours?

Answer 52

Malignant --> cancerous & can spread by metastasis Benign --> non-cancerous

Question 53

Main characteristics of benign tumours

Answer 53

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

Question 54

Why doe benign tumours not spread by metastasis?

Answer 54

Cell adhesion molecules stick cells together

Question 55

Main characteristics of malignant tumours

Answer 55

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

Question 56

Describe the function of tumour suppressor genes

Answer 56

Code for proteins that inhibit / slow the cell cycle OR causes self-destruction of potential tumour cells