Gene Expression

Describe how a mutation can create a non-functional protein

• Change in DNA base sequence

• Changes the amino acid sequence of the protein

• Changes the hydrogen bonding and ionic bonding between amino acids

• Changes the tertiary structure

When are mutations most likely to occur? Name the stage of cell cycle when this would occur.

• Mutation occur at random during DNA replication

• DNA replication takes place during interphase

Mutagens increase the rate of mutation - name 2 mutagens

• High Energy Radiation eg. UV light, X-rays

• Chemicals eg. benzene and asbestos

5-bromouracil is a base analog. How might 5-bromouracil causes a mutation during DNA replication and cause a non-functional protein

• 5-bromouracil is similar in shape to thymine

• 5-bromouracil complementary base pairs with adenine instead of thymine

• This changes the DNA base sequence

• Changes the amino acid sequence

• Change in hydrogen bonding and tertiary structure

Types of mutation

• Substitution

• Addition

• Deletion

• Inversion

• Duplication

• Translocation

Substitution mutation

When one base is changed for a different base. eg. A swapped with C

Addition mutation

When one or more base is inserted into the DNA base sequence. Causes a frame shift

Deletion mutation

When one or more base is removed from the DNA base sequence. Causes a frame shift

Inversion mutation

A sequence of bases is reversed. eg. CAAT becomes TAAC (not a frame shift)

Duplication mutation

A sequence of bases repeated. eg. CAT becomes CATCATCAT

Causes a frame shift

Translocation mutation

A sequence of bases is moved from one location on the genome to another

Types of Substitution Mutation

Mis-sense mutation (one base)

Silent mutation

Nonsense (stop)

Mis-sense mutation

Changes one amino acid

Changes the tertiary structure if the amino acid is involved in hydrogen bonding

Silent mutation

Does not change the amino acid sequence

So no effect on the polypeptide as DNA code is degenerate

Nonsense (stop mutation)

Changes the amino acid sequence

So polypeptide is shorter

Describe the effect a frame shift mutation has on a DNA base sequence and a polypeptide

• All triplet codes change from the point of mutation

• All amino acids change from the point of mutation

How does a cell differentiate and become specialised?

Certain genes in a cell are expressed to produce the specific proteins the cell needs

What does it mean when a gene is expressed

DNA (gene) is transcribed and translated into a protein

Give an example of a certain gene, which is only expressed in a particular specialised cell

• The haemoglobin gene is only expressed in red blood cells

• The antibody gene is only expressed in plasma cells

Can one type of specialised cell turn into a different specialised cell?

No, once a cell has differentiated into a specialised cell, it will not divide and it will stay specialised

What are stem cells? (3 points)

• Unspecialised cells

• Can keep dividing

• Differentiate into specialised cells

Types of stem cells

• Totipotent: can divide and differentiate into any type of body cell

• Pluripotent: can divide and differentiate into most types of body cell

• Multipotent: can divide and differentiate into a limited number of cell types

• Unipotent: can divide and differentiate into only one cell type

When are the stem cells present during the organisms life?

• Totipotent: occurs only for a limited time in early mammalian embryos

• Pluripotent: found in the later embryos

• Multipotent: found in mature mammals (after birth)

• Unipotent: cardiomycytes (heart muscle cells)

How can stem cells be used in the treatment of disease?

Stem cells can be transplanted to divide and differentiate into the cell type required. eg. nerve cells for spinal injury

Treating Leukemia with stem cells

• Bone marrow is used from a close relative to reduce chance of rejection

• The stem cells continuously divide and differentiate to produce healthy white blood cells

• This gives a long term treatment

• No cancerous white blood cells are produced

Types of stem cells used in medicine

• Adult stem cells- from same individual or close relative

• Embryonic stem cells- from an embryo

Advantages of adult stem cells

• No ethical issues

• Less chance of rejection (same / similar DNA)

Disadvantages of adult stem cells

• Multipotent- differentiates into a limited number of cell types

• Difficult to isolate

Advantages of embryonic stem cell

• Pluripotent- can divide and differentiate into almost all cell types

• Easy to isolate- uses embryo from IVF

Disadvantages of embryonic stem cells

• Unethical?

• Higher chance of rejection

What does IPs stand for

Induced Pluripotent Stem Cells

What are IPs cells

• Specialised cells are removed from a patient and factors added to make cell pluripotent

• The IPs cells then divide and differentiates into the desired cell type

• The specialised cells are transplanted back into the patient

What are the advantages of IPs cells

• Can differentiate into any cell type (pluripotent)

• It’s long term

• No ethical issues as using own cells

• Less chance of rejection

Explain how transcription factors control transcription in eukaryotes

• Transcription factors are protein

• They move from the cytoplasm to the nucleus

• They bind to a promoter (specific base sequence) on DNA

• This stimulates RNA polymerase

• Gene is transcribed and produces mRNA

Explain how oestrogen can act as a transcription factor

• Oestrogen is lipid soluble so crosses the phospholipid bilayer by diffusion

• Oestrogen binds to complementary protein receptor in the cytoplasm

• Receptor/oestrogen complex is a transcription factor. It binds to a promoter on DNA

• This stimulates RNA polymerase to transcribe the gene and produce mRNA

What is the link between oestrogen and cancer

Increased oestrogen concentration can increase the risk of breast cancer

How does increased oestrogen increase the risk of breast cancer

• Oestrogen can cause breast cells to divide more

• More likely that mutations occur when DNA replicates

• Faster division of cancerous cells will produce tumours more quickly

What do transcription factors cause

They cause transcription and therefore the expression of certain genes into protein

What does RNA interference prevent

RNA interference prevents mRNA bring translated into protein

What is the full meaning of siRNA

Small interfering RNA

Steps of RNA interference

• siRNA has a specific complementary base sequence to the target mRNA .

• The siRNA now binds to mRNA molecules by complementary base pairing.

• The mRNA is destroyed

• The mRNA can no longer be used in translation and is broken down by enzymes

What is the use of miRNA

MicroRNA can be used to target and destroy mRNA

What is the difference between miRNA and siRNA

miRNA is not fully complementary and not specific to one mRNA and therefore targets more than one type of mRNA unlinke siRNA which targets one

What is the full meaning of miRNA

MicroRNA

What is cancer caused by

Mutations in the genes which controls mitosis

What does the mutation in genes that controls mitosis lead to

Uncontrolled cell division, forming a mass of cells called a tumour

What are the types of tumours

Malignant

Benign

Malignant - cancerous

Metastatis: cell can break off and spread to other parts f the body forming a tumour elsewhere

Benign- non cancerous

No metastasis: cells do not spread to other parts of the body

What are the 2 genes that control cell division and define them

Tumour suppressor genes: code for proteins which prevent cell division

Proto-oncogenes: code for proteins which stimulate cell division

What happens when there’s a mutation in the tumour suppressor genes?

Stops the formation of proteins which prevent mitosis. This leads to uncontrolled cell division

What happens when there’s a mutation in the proto-oncogenes?

Mutates to oncogenes. Forms more protein which cause cell division. This leads to uncontrolled cell division

Methods which control gene expression

• Transcription factors

• RNA interference

• Epigenetics

Define epigenetics

Heritable changes in gene function without changes to the DNA base sequence

Methylation of DNA

• Methyl groups are added to DNA

• Transcription factors cannot bind to the promotor on DNA

• RNA polymerase is not activated

• Gene is not transcribed (and translated)

Acetylation of histone proteins

• The addition of acetyl groups to histone proteins makes chromatin less condensed

• Transcription factors can bind to the promotor

• RNA polymerase is activated

• Transcription does occur

Which type of gene can lead to tumour formation when methylated?

Tumour suppressor gene

Which type of gene can lead to tumour formation when it is less methylated?

Oncogene

Explain how increased methylation of tumour suppressor genes can lead to the formation of a tumour

• Methyl group could be added to a tumour suppressor gene

• Transcription factor cannot bind to promotor on DNA

• RNA polymerase is not activated

• No transcription

• (Protein which reduce cell division are not produced)

• Leading to uncontrolled cell division