3.8 The control of gene expression

What is a gene mutation?

● A change in the base sequence of DNA (on chromosomes)

● Can arise spontaneously during DNA replication (interphase)

What is a mutagenic agent?

A factor that increases rate of mutation, eg. ultraviolet (UV) light or alpha particles

Explain how a gene mutation can lead to the production of a non-functional protein or enzyme (general)

1. Changes sequence of base triplets in DNA so changes sequence of codons on mRNA

2. So changes sequence of amino acids in the encoded polypeptide

3. So changes position of hydrogen / ionic / disulphide bonds (between amino acids)

4. So changes tertiary structure (shape) of protein

5. Enzymes - active site changes shape so substrate can’t bind, enzyme-substrate complex can’t form

Substitution

A base / nucleotide is replaced by a different base / nucleotide in DNA

Addition

1 or more bases / nucleotides are added to the DNA base sequence

Deletion

1 or more bases / nucleotides are lost from the DNA base sequence

Duplication

A sequence of DNA bases / nucleotides is repeated / copied

Inversion

A sequence of bases / nucleotides detaches from the DNA sequence, then rejoins at the same position in the reverse order

Translocation

A sequence of DNA bases / nucleotides detaches and is inserted at a different location within the same or a different chromosome

Explain why not all gene mutations affect the order of amino acids

● Some substitutions change only 1 triplet code / codon which could still code for the same amino acid

○ As the genetic code is degenerate (an amino acid can be coded for by more than one triplet)

● Some occur in introns which do not code for amino acids as they are removed during splicing

Explain why a change in amino acid sequence is not always harmful

● May not change tertiary structure of protein (if position of ionic / disulphide / H bonds don’t change)

● May positively change the properties of the protein, giving the organism a selective advantage

Explain what is meant by a frameshift

● Occurs when mutations (addition, deletion, duplication or translocation) change the number of nucleotides / bases by a number not divisible by 3

● This shifts the way the genetic code is read, so all the DNA triplets / mRNA codons downstream from the mutation change (so significant effects)

• Effects on the encoded polypeptide are significant

Explain how mutations can lead to production of shorter polypeptides

● Deletion or translocation → triplet(s) / codon(s) missing so amino acid(s) missing

● Substitution, addition, deletion, duplication, inversion or translocation → premature stop triplet / codon (doesn’t code for amino acids; terminates translation) so amino acids missing at end of polypeptide

What are stem cells?

Undifferentiated / unspecialised cells capable of:

1. Dividing (by mitosis) to replace themselves indefinitely

2. Differentiating into other types of (specialised) cells

Describe how stem cells become specialised during development

● Stimuli lead to activation of some genes (due to transcription factors - see 8.2.2)

● So mRNA is transcribed only from these genes and then translated to form proteins

● These proteins modify cells permanently and determine cell structure / function

Describe totipotent cells

● Occur for a limited time in early mammalian embryos

● Can divide AND differentiate into any type of body cell (including extra-embryonic cells eg. placenta)

Describe pluripotent cells

● Found in mammalian embryos (after first few cell divisions)

● Can divide AND differentiate into most cell types (every cell type in the body but not placental cells)

Describe multipotent cells

● Found in mature mammals

● Can divide AND differentiate into a limited number of cell types

Example: multipotent cells in bone marrow can divide and differentiate into different types of blood cell

Describe unipotent cells, using an example

● Found in mature mammals

● Can divide AND differentiate into just one cell type

Example: unipotent cells in the heart can divide and differentiate

into cardiomyocytes (cardiac muscle cells)

Explain how stem cells can be used in the treatment of human disorders

● Transplanted into patients to divide in unlimited numbers

● Then differentiate into required healthy cells (to replace faulty / damaged cells)

Examples:

● Potential treatment of Type 1 diabetes by creating healthy islet cells that produce insulin

● Bone marrow stem cell transplant for sickle cell disease / blood cancers

1. Destroy patient’s bone marrow before treatment → so no faulty cells are produced

2. Transplant stem cells from healthy person → divide and differentiate into healthy cells

Explain how induced pluripotent stem (iPS) cells are produced

1. Obtain adult somatic (body) cells (non-pluripotent cells or fibroblasts) from patient

2. Add specific protein transcription factors associated with pluripotency to cells so they express genes associated with pluripotency (reprogramming)

○ Transcription factors attach to promoter regions of DNA, stimulating or inhibiting transcription

3. Culture cells to allow them to divide by mitosis

• Once made, iPS cells can divide and differentiate into healthy cells to be transplanted into the same patient

Evaluate the use of stem cells in treating human disorders

For :

✓ Can divide and differentiate into required healthy cells, so could relieve human suffering by saving lives and improving quality of life

✓ Embryos are often left over from IVF and so would otherwise be destroyed

✓ iPS cells unlikely to be rejected by patient’s immune system as made with patient’s own cells

✓ iPS cells can be made without destruction of embryo and adult can give permission

Against:

X Ethical issues with embryonic stem cells as obtaining them requires destruction of an embryo and potential life (embryo cannot consent)

X Immune system could reject cells and immunosuppressant drugs are required

X Cells could divide out of control, leading to formation of tumours / cancer

What are transcription factors?

● Proteins which regulate (stimulate or inhibit) transcription of specific target genes in eukaryotes

● By binding to a specific DNA base sequence on a promoter region

Describe how transcription can be regulated using transcription factors

1. Transcription factors move from cytoplasm to nucleus

2. Bind to DNA at a specific DNA base sequence on a promoter region (before / upstream of target gene)

3. This stimulates or inhibits transcription (production of mRNA) of target gene(s) by helping or preventing RNA polymerase binding