Control of gene expression and epigenetics

Question 1

What are the 3 possible consequences of a substitution mutation?

Answer 1

• premature stop codon
• different amino acid coded for
• no change due to degeneracy of genetic code (silent)

Question 2

Why do addition/deletion mutations have a greater effect than substitution mutations?

Answer 2

They result in a frameshift - when the genetic code is shifted left/right by one letter so the gene is read in the wrong 3 base groups, so all the amino acids coded for will be different - this will lead to the production of a non-functional protein which will largely effect the phenotype

Question 3

What are the other types of mutations?

Answer 3

• addition
• duplication - one or more bases are repeated resulting in a frameshift
• inversion - the order of a group of bases is reversed
• translocation - a base sequence on one chromosome is separated from one chromosome and inserted into another chromosome

Question 4

What are the causes of mutations?

Answer 4

• high energy ionising radiation eg. X-rays/uv light - disrupt the structure of DNA
• chemicals eg. asbestos - alter the structure of DNA and interfere with transcription

Question 5

What are mutagenic agents?

Answer 5

Factors that increase the rate of mutations

Question 6

How might mutations be useful to an organism?

Answer 6

they may produce the genetic diversity needed for natural selection - this will give an organism advantageous alleles which make it more likely to survive in its environment, outcompete others and pass on the alleles to offspring

Question 7

In humans, body cells are all derived from mitotic divisions of the zygote therefore all contain the same genes. So why can’t all cells produce the same hormones?

Answer 7

Although all cells contain the same genes, only certain genes are expressed (switched on) in a cell at a certain time

Question 8

What are totipotent cells?

Answer 8

cells such as fertilised eggs which can mature into any kind of body cell

Question 9

How do cells become specialised?

Answer 9

Because only part of the DNA of a cell is translated into proteins, and the cell will therefore only produce proteins required to carry out its specialised function. Therefore only some of the genes are expressed

Question 10

What are the ways in which genes are prevented from expressing themselves?

Answer 10

• preventing transcription and therefore preventing the production of mRNA
• preventing translation

Question 11

Why can xylem cells not specialise into other cells?

Answer 11

Because once they are matured, they lose their nuclei - the nucleus contains the genes and therefore without these genes the cells cannot develop into other cells

Question 12

What are stem cells?

Answer 12

undifferentiated dividing cells that can divide to form an identical copy of themselves - they can differentiate into any type of cell

Question 13

Where do stem cells originate from?

Answer 13

• embryonic stem cells
• umbilical cord blood stem cells
• placental stem cells
• adult stem cells

Question 14

What are the types of stem cells?

Answer 14

• totipotent stem cells - found in the early embryo and can differentiate into any type of cell, as the zygote divides and matures cells become slightly more specialised into:
• pluripotent stem cells - found in embryos and can differentiate into almost every type of cell, but not all
• multipotent stem cells - found in adults and can differentiate into a limited number of specialised cells eg. stem cells in bone marrow
• unipotent stem cells - can only differentiate into a single type of cell

Question 15

What are induced pluripotent stem cells?

Answer 15

• a type of pluripotent cell that is produced from adult somatic cells using protein transcription factors, the unipotent cell may be any type of body cell which is genetically altered in a lab to acquire characteristics of embryonic stem cells by switching on genes that were switched off during specialisation

Question 16

Why are iPS cells important for the future?

Answer 16

they can divide to provide a limitless supply, therefore can replace embryonic stem cells in medical research and treatment, so overcomes ethical issues

Question 17

How can pluripotent stem cells be used in treating human disorders?

Answer 17

• regrow damaged tissues eg. skin grafts
• blood cells for leukemia
• nerve cells for Parkinson’s disease

Question 18

What are totipotent cells?

Answer 18

cells that can mature into any type of body cell - during development, they will only translate part of their DNA resulting in cell specialisation

Question 19

What is a transcriptional factor?

Answer 19

a protein necessary to initiate transcription, this is what allows cells to become specialised because only certain regions of DNA will be transcripted

Question 20

How does oestrogen act as a transcription factor?

Answer 20

• oestrogen is a small, lipid-soluble molecule and therefore can easily diffuse into the cytoplasm through the phospholipid bilayer
• oestrogen enters the cell and binds to the complementary binding site on the transcription factor
• when oestrogen binds, it changes the shape of the DNA binding site, releasing the inhibitor which causes the DNA binding site to change shape and becomes complementary to the DNA promoter
• transcription factor enters the nucleus through nuclear pores and binds to DNA at the promoter, stimulating RNA polymerase and therefore transcription

Question 21

What is epigenetics?

Answer 21

involves hertiable changes in gene function, without changes to the base sequence of DNA. These changes are caused by changes in the environment that inhibit transcription by:
- increased methylation of DNA
- decreased acetylation of histones

Question 22

What is the epigenome?

Answer 22

all of the chemical tags that are added to the DNA histones which determines the shape of the DNA-histone complex

Question 23

How (simply) and why does the epigenome change?

Answer 23

The chemical tags can respond to changes in the environment - this adjusts how tightly packed the DNA is - tightly packed DNA cannot be accessed to be transcribed so this switches the gene off, whereas loosely packed DNA exposes DNA so it can easily be transcribed and the gene will be switched on

Question 24

How does decreased acetylation of associated histones affect the gene expression?

Answer 24

• acetyl coA donates a negatively charged acetyl group to the histones which attaches to the histone tails
• decreasing acetylation increases the positive charges on histones which increases their attraction to the negatively charged phosphate group in DNA
• this leads to a stronger association between DNA and histones, meaning the DNA is not accessible to transcription factors
• this means mRNA production cannot be stimulated so the gene is switched off

Question 25

How does increased methylation of DNA affect the gene expression?

Answer 25

- methyl group is added to the cytosine bases on DNA - this will inhibit transcription because it blocks binding sites at the promoter on DNA, preventing transcriptional factors from binding - attracts proteins which cause the DNA-histone complex to condense and become inaccessible to transcription factors

Question 26

What effects do acetylation and methylation have on gene expression?

Answer 26

methylation masks. acetylation allows

Question 27

What conditions are needed for a gene to be active?

Answer 27

- acetylated histones - unmethylated - not condensed DNA-histone complex

Question 28

How can epigenetic therapy be used to treat diseases?

Answer 28

- using drugs to inhibit enzymes that cause DNA methylation - reactivates silenced genes - develop diagnostic tests that can identify the level of DNA methylation and histone acetylation at an early stage

Question 29

What is the effect of RNA interference on gene expression?

Answer 29

- an enzyme cuts large double-stranded molecules of RNA into smaller sections called siRNA (small interfering RNA) - one of the siRNA strands combines with an enzyme - the siRNA molecule guides the enzyme to an mRNA molecule through complementary base pairing - the enzyme cleaves mRNA into smaller pieces, meaning that it is no longer able to be translated into a polypeptide, and therefore the gene is switched off

Question 30

How can siRNA be used to treat diseases?

Answer 30

- can be used to silence mutated genes that may cause disease by cleaving the mRNA that the harmful protein is produced from

Question 31

What is the difference between benign and malignant tumours?

Answer 31

benign = smaller, well-differentiated, non-cancerous - they have no metastasis and are surrounded by a capsule so cannot spread around the body malignant = larger, poorly-differentiated and cancerous - they have metastasis and no capsule so can spread around the body

Question 32

What is a tumour?

Answer 32

a mass of cells that are a result of rapid, uncontrollable cell division

Question 33

What is metastasis?

Answer 33

when cancerous cells spread elsewhere in capillaries/bloodstream

Question 34

How do tumours develop and how can this lead to metastasis?

Answer 34

- mutated cell continually divides uncontrollably as it does not recognise signals to stop which causes a small primary tumour to develop - as the tumour mass grows, blood and lymph vessels grow which provides more nutrients for further growth - a few cells break away into a capillary which allows the cancerous cells to spread elsewhere (metastasis) - cells are carried in the blood to new organs where they leave the capillaries - start of a metastatic tumour when these cells divide continuously, producing a secondary tumour - some cells can also break off into lymph glands to form gland tumours

Question 35

What can unipotent stem cells be used to make?

Answer 35

cardiomyocytes - heart muscle cells

Question 36

How do transcription factors cause specialisation?

Answer 36

without the binding of a transcription factor, the gene will remain inactive so the protein will not be translated - only certain genes will be switched on

Question 37

What are the active and silent regions of DNA called?

Answer 37

active = euchromatin silent = heterochromatin

Question 38

How might tumours develop (reasons)?

Answer 38

- gene mutations in the tumour suppressor genes and/or oncogenes - abnormal methylation of tumour suppressor genes and/or oncogenes - increased oestrogen concentrations affecting transcription

Question 39

What are proto-oncogenes and oncogenes?

Answer 39

- proto-oncogenes create proteins which are involved in the initiation of DNA replication and mitosis - oncogenes are mutated versions of protons-oncogenes - they can make this process permanently activated which results in uncontrollable cell division

Question 40

How do proto-oncogenes stimulate DNA replication?

Question 41

How do oncogenes lead to uncontrolled cell division?

Answer 41

- can cause the receptor protein on the cell membrane to be permanently activated so cell division is activated even in the absence of growth factors - code for a growth factor that is produced in excessive amounts so constantly stimulates division

Question 42

What are tumour suppressor genes and what happens when they become mutated?

Answer 42

- produce proteins which slow cell division and cause cell death if DNA copying errors are detected - a mutation means that the proteins are not produced, so cell division would continue uncontrollably and mutated cells would not be identified or destroyed

Question 43

How does methylation affect the tumour suppressor gene?

Answer 43

prevents transcription factors from binding, so tumour suppressor genes cannot be transcribed meaning they are switched off and not expressed, this results in uncontrolled cell division

Question 44

What is a promoter region?

Answer 44

the sequence on DNA that a transcription factor binds to

Question 45

How does increased oestrogen increase risk of cancer?

Answer 45

oestrogen acts as a transcription factor so can bind to a gene and initiate transcription, if this is a porto-oncogene then it will be permanently turned on activating cell division

Question 46

How does methylation affect cancer genes?

Answer 46

- Hypermethylation of tumour suppressor genes prevents them from being active, this stops the production of proteins that would normally inhibit cell division, and cells divide unchecked to form tumours - Hypomethylation of proto-oncogenes leads to their activation as oncogenes. This activation promotes excessive cell division and tumour growth, especially as some oncogenes code for growth factors that stimulate further cell division