Biology - Chapter 20: Gene Expression

6 types of mutations

Substitution, addition, deletion, inversion, duplication and translocation

3 possible consequences of a substitution mutation

1. A stop codon forms and production of the polypeptide is stopped prematurely

2. A different codon forms, which codes for a different amino acid

3. A different codon forms, which codes for the same amino acid

When might an addition mutation have less of an effect? Why?

When 3 bases (or a multiple of 3 bases) are added as there will be no frameshift

Cell differentiation

The process by which each cell develops into a specialised structure suited to the role that it will carry out

Where are all the cells in an organism derived from?

A zygote

Why can only certain types of cells produce certain proteins?

Although all cells contain all genes, only certain genes are expressed in any one cell at any one time

Totipotent cells

Cells that can divide and produce any type of body cell

Why don’t cells make all the proteins possible?

It would waste energy and resources

2 ways genes are prevented from being expressed

1. Preventing transcription (i.e. the production of mRNA)

2. Preventing translation

Stem cells

Cells that have the ability to differentiate into other cells

4 sources of stem cells

1. Embryonic stem cells

2. Umbilical cord blood stem cells

3. Placental stem cells

4. Adult stem cells

4 types of stem cells

1. Totipotent

2. Pluripotent

3. Multipotent

4. Unipotent

2 examples of totipotent stem cells

Early embryos and zygotes

Pluripotent stem cells

Cells that can differentiate into almost any type of cell

2 examples of pluripotent stem cells

Embryonic stem cells and fetal stem cells

Multipotent stem cells

Cells that can differentiate into a limited number of specialised cells

2 examples of multipotent stem cells

Adult stem cells and umbilical cord stem cells

Unipotent stem cells

Cells that can only differentiate into a single type of cell

Where are unipotent stem cells derived from?

Multipotent stem cells

Induced pluripotent stem cells

A type of pluripotent stem cell that is produced from somatic cells

iPS

Induced pluripotent stem cell

Why are iPS special?

They are capable of self-renewal, so could potentially divide indefinitely to provide a limitless supply

What might pluripotent stem cells be used for?

To regrow tissues that have been damaged

Transcriptional factors

Molecules that switch genes on so that transcription of the gene can begin

How do transcriptional factors affect transcription? (5)

1. The transcriptional factor has a site that binds to a specific base sequence of DNA in the nucleus

2. When it binds, it causes this part of the DNA base sequence to begin transcription

3. mRNA is produced and it is used to produce a polypeptide

4. If the gene is not being expressed, the site of the transcriptional factor complimentary to the DNA base sequence is not active

5. This means it cannot cause transcription and protein synthesis

How does oestrogen switch on genes? (5)

1. It diffuses across the phospholipid bilayer

2. It binds to the complementary receptor on a transcriptional factor

3. This activates the transcriptional factor as its DNA binding site is now complimentary to and can bind to DNA

4. The transcriptional factor enters the nucleus and binds to the specific base sequence on DNA

5. This stimulates transcription of the gene

Epigenetics

Heritable changes in gene function without changing the base sequence of DNA

Epigenome

A layer of chemical tags that cover DNA and histones

What does the epigenome do?

It determines the shape of the DNA-histone complex, which affects what genes are switched on or off

Epigenetic silencing

When the epigenome keeps inactive genes in a tightly-packed arrangement, ensuring that they cannot be read

Is the epigenome fixed or flexible? Why?

Flexible - its chemical tags respond to environmental changes

Somatic cells

Cells in the body other than the sperm and egg cells

What might environmental signals cause proteins to change? (2)

1. The acylation of histones, leading to the activation or inhibition of a gene

2. The methylation of DNA by attracting enzymes that can add or remove methyl groups

What happens when the association of histones with DNA is strong? (3)

1. The DNA-histone complex is more condensed

2. The DNA is not accessible by transcription factors, so cannot initiate the production of mRNA

3. The gene is switched off

What happens when the association of histones with DNA is weak? (3)

1. The DNA-histone complex is less condensed

2. The DNA is accessible by transcription factors, so can initiate the production of mRNA

3. The gene is switched on

What happens as a result of the decreased acetylation of associated histones? (4)

1. Fewer acetyl groups bond to the R groups in histones, so the positive charges on histones remain (so increase)

2. This increases their attraction to the phosphate groups of DNA

3. This makes the association between DNA and histones stronger, so the DNA is not accessible to transcription factors

4. mRNA production is not initiated - the gene is switched off

Acetylation

The process whereby an acetyl group is transferred to a molecule

Deacetylation

The process by which an acetyl group is removed from a molecule

What group donates the acetyl group in acetylation?

Acetylcoenzyme-A

How does the increased methylation of DNA inhibit the transcription of genes? (2)

1. It prevents the binding of transcriptional factors to DNA

2. It attracts proteins that condense the DNA-histone complex (by inducing the deacetylation of histones), making the DNA inaccessible to transcription factors

Methylation

The addition of a methyl group to a molecule

In methylation, what is the methyl group added to?

The cytosine bases of DNA

What is oestrogen?

A steroid hormone

What happens when acetyl groups are added to DNA-histone complexes? (3)

They bind to the R groups of the histones, removing the positive charge on NH₃⁺. This reduces the attraction between the phosphate backbone and the R group, so DNA loosens from the histone.

Give three characteristic features of stem cells.

1. Undifferentiated cells

2. Can differentiate into other cells

3. Can keep dividing

What is the effect of epigenetic changes on mutations? Why?

They can increase the incidence of mutations e.g. if they cause an increase in the methylation of protective genes so damaged DNA base sequences are not repaired and can lead to cancer

How might epigenetic therapy be used to treat diseases? (2)

1. Drugs may be designed that inhibit enzymes involved in acetylation or methylation (must be specific to cancer cells)

2. They can be used to develop diagnostic tests that can detect the early stages of diseases

How does siRNA affect gene expression? (5)

1. Enzyme cuts large double-stranded RNA into siRNA

2. One of the two strands combines with an enzyme

3. siRNA molecule guides the enzyme to an mRNA molecule by pairing up its bases with the complementary section on mRNA

4. Enzyme cuts mRNA into smaller strands

5. mRNA can no longer be translated into a polypeptide - gene has not been expressed

siRNA

Small Interfering RNA

Cancer

A group of diseases caused by damage to the genes that regulate mitosis and the cell cycle

2 types of tumours:

Malignant (cancerous) and benign (non-cancerous)

Benign tumours vs malignant tumours (9)

Similarities:

Both grow to a large size

Differences:

1. Grow very slowly vs rapidly

2. Relatively normal nucleus vs larger and darker (abundance of DNA)

3. Specialised cells vs unspecialised cells

4. Cells stick together and remain within tissue - primary tumours (due to adhesion molecules produced) vs Cells spread to other regions of the body by metastasis, don’t produce adhesion molecules - form secondary tumours

5. Tumours surrounded by capsule so compact structure vs No capsule so tumours can grow finger-like projections into surrounding tissue

6. Less likely to be life-threatening but may affect functioning of vital organs vs More likely to be life-threatening (replacement of normal tissue by abnormal)

7. Localised effects on body vs Systemic effects

8. Usually removed by surgery only vs Radiotherapy, chemotherapy and/or surgery

9. Rarely reoccur after treatment vs more frequently reoccur after treatment

2 types of genes involved in cancer

Oncogenes and tumour suppressor genes

How do oncogenes form?

As a result of mutations to proto-oncogenes

What happens if proto-oncogenes are mutated to form oncogenes? (1+2+1)

It becomes permanently activated so:

1. Receptor protein on CSM can be permanently activated so cell division is switched on, even without growth factors

2. Oncogene may code for a growth factor that is then produced in excessive amounts, stimulating cell division

Cells divide too rapidly and a tumour or cancer develops

What do tumour suppressor genes do? (3)

1. Slow down cell division

2. Repair mistakes in DNA

3. Tell cells when to die / undergo apoptosis

What might happen if a tumour suppressor gene is inactivated?

1. The mutation makes the gene become inactive

2. It stops inhibiting cell division, so cells divide uncontrollably

How can the abnormal methylation of tumour suppressor genes result in the development of tumours? (4)

1. Increased methylation

2. The tumour suppressor gene is not transcribed and is inactive

3. Proteins that cause cells to undergo apoptosis and that repair damaged DNA are not produced - these processes do not occur

4. This results in uncontrollable cell division and the formation of a tumour

How can the abnormal methylation of oncogenes result in the development of tumours? (3)

1. Decreased methylation means the oncogene is transcribed more and is active

2. This means cell division takes place at an increased rate

3. This results in the formation of a tumour

How can increased oestrogen concentrations affect the development of some breast cancers? (6)

1. After menopause, the fat cells of the breast tissue produce more oestrogen

2. This could cause a gene that promotes transcription to be switched on, so more transcription and more cell division

3. This causes a tumour to develop

4. The tumour then also increases oestrogen concentration

5. WBCs are drawn to the tumour, which also causes an increase in oestrogen concentration

6. This causes the tumour to develop more

Bioinformatics

The science of collecting and analysing complex biological data

Why was it possible to sequence the entire genome so quickly?

Bioinformatics - the use of computers to read, store and organise biological data at a faster rate than before as well as to analyse and interpret the data

How is the complete DNA base sequence of an organism determined?

By using whole-genome shotgun sequencing - DNA is cut into many small, easily sequenced sections, then computer algorithms are used to align overlapping segments to assemble the entire genome

Why can genomes be sequenced more rapidly as time goes on?

Because sequencing methods are continuously updated and the processes involved are becoming increasingly automated

Why is it easier to determine the proteome of prokaryotic organisms from the genome compared to the proteome of eukaryotic organisms? (2)

1. The vast majority of prokaryotes have just one circular piece of DNA not associated with histones

2. There are no non-coding portions of DNA, unlike in eukaryotic cells

How might the knowledge of the genome of an organism be applied to produce vaccines against pathogens?

The proteome of an organism could be identified, which could then be used to identify potential antigens for use in vaccine production

In more complex organisms, why might it be harder for knowledge of the genome to be translated to the proteome?

Because of the presence of non-coding DNA and regulatory proteins

What must happen for a gene to be transcribed more? (2)

1. Transcription factors will bind to promoter region

2. RNA polymerase will be stimulated

When testing the effect of a new drug (e.g. on cancer), why would you give the control group the older drug?

it would not be ethical to fail to treat their disease (e.g. cancer)

How might single-stranded DNA molecules be used to reduce concentrations of a protein? (3)

1. DNA is complementary to the mRNA that codes for the protein

2. The DNA binds to the mRNA

3. This prevents translation

How does siRNA work? (Exam q, 2)

1. siRNA destroys mRNA

2. This prevents the mRNA from being translated