Gene Expression & Control

Gene expression begins when proteins bind to a specific DNA sequence to control whether a gene is transcribed. These proteins are called:

• Abacterial restriction endonucleases
• BDNA-dependent DNA polymerases
• Cribosomal RNA-binding proteins
• Dtranscription factors✓

Answer: Transcription factors are proteins that bind to specific DNA sequences (such as promoters/enhancers) and either stimulate or inhibit RNA polymerase, controlling the rate of transcription of target genes.

Oestrogen is a steroid hormone that switches on the transcription of certain genes. By what mechanism does it do this?

• AIt binds to a receptor on the cell-surface membrane, activating a second messenger such as cyclic AMP that switches on the target genes
• BIt binds directly to RNA polymerase in the cytoplasm and carries the enzyme through a nuclear pore to the promoter region of the target gene
• CIt is converted into messenger RNA (mRNA) inside the nucleus
• DBeing lipid-soluble, it diffuses into the cell and binds a receptor, and the hormone-receptor complex acts as a transcription factor✓

Answer: Oestrogen is lipid-soluble, so it diffuses through the phospholipid membrane and binds to a specific receptor in the cytoplasm. The oestrogen-receptor complex moves to the nucleus and acts as a transcription factor, binding DNA and stimulating transcription of target genes.

Increased methylation of DNA (addition of methyl groups to cytosine bases) in the promoter region of a gene usually has what effect on that gene?

• AIt prevents transcription, switching the gene off✓
• BIt increases transcription of the gene
• CIt changes the base sequence of the gene
• DIt causes the gene to be deleted from the genome

Answer: Increased methylation of the promoter typically inhibits transcription (gene silencing), often by preventing transcription factor binding and promoting tighter chromatin. It is an epigenetic change: the base sequence is unchanged.

Decreased acetylation of histone proteins affects gene expression. Why does removing acetyl groups from histones tend to reduce transcription?

• AIt changes the DNA base sequence wound around the histones, so the genes are mis-transcribed
• BIt causes the histones to move out of the nucleus (histone eviction), leaving naked DNA
• CIt denatures RNA polymerase, which then detaches from the DNA
• DHistones become more positively charged, bind DNA more tightly and condense the chromatin, reducing access for transcription factors✓

Answer: Acetyl groups reduce the positive charge on histones, loosening their association with the negatively charged DNA. Removing acetyl groups (deacetylation) increases histone positive charge, condensing chromatin so that genes are less accessible and transcription decreases.

In RNA interference (RNAi), how do small interfering RNA (siRNA) molecules reduce the expression of a target gene?

• AThey bind to the promoter region of the gene itself and physically block the transcription factors from attaching to the DNA double helix
• BThey add methyl groups to the cytosine bases of the gene, so the chromatin condenses and transcription of that gene is shut down
• CThey guide an enzyme complex to a complementary mRNA, which is then cut up and degraded so it is not translated✓
• DThey speed up translation of the mRNA, giving more protein per transcript

Answer: A single strand of siRNA, combined with proteins, binds by complementary base pairing to a target mRNA. This targets the mRNA for cleavage and degradation, preventing it from being translated and so reducing expression of that gene (post-transcriptional silencing).

A substitution mutation occurs in the third base of a codon but the amino acid coded for does not change. This is possible because the genetic code is:

• Anon-overlapping (each base belongs to a single codon, so neighbouring triplets do not share bases)
• Buniversal (the same codons are used across living organisms)
• Cdegenerate (more than one codon can code for the same amino acid)✓
• Dread in triplets (each amino acid is specified by a sequence of three bases)

Answer: The genetic code is degenerate: most amino acids are specified by more than one codon, with variation often in the third base. A substitution at that position can therefore be a silent mutation, producing the same amino acid.

Why does a single base deletion near the start of a gene's coding sequence usually have a much more severe effect on the protein than a single base substitution?

• AA deletion removes a whole amino acid from the finished polypeptide, so the chain is one residue shorter but otherwise unchanged
• BA deletion causes a frameshift, altering every codon downstream of the mutation✓
• CA substitution leaves the amino acid sequence unchanged, because the third base of a codon is ignored during translation
• DA deletion only affects non-coding regions (introns)

Answer: Deleting (or inserting) a single base shifts the reading frame, so all subsequent triplets are read differently. This frameshift usually changes many amino acids and often introduces a premature stop codon, whereas a substitution affects at most one codon.

A proto-oncogene normally codes for a protein that stimulates cell division in a controlled way. A mutation can convert it into an oncogene. What is the typical consequence?

• AThe gene becomes permanently active or overactive, causing uncontrolled cell division✓
• BCell division stops completely
• CThe cell loses the ability to repair damaged DNA, so mutations accumulate throughout the genome and division halts
• DThe cell undergoes programmed cell death immediately

Answer: An oncogene is a mutated, permanently activated proto-oncogene whose product over-stimulates the cell cycle, driving uncontrolled mitosis and tumour formation. Loss of cell-division control (not its cessation) is the key feature.

How can the inactivation of a tumour-suppressor gene (such as by mutation or hypermethylation of its promoter) contribute to cancer?

• AIt increases production of the proteins (such as p53) that slow the cell cycle
• BIt removes the normal 'brake' on cell division and on apoptosis, allowing uncontrolled growth✓
• CIt directly converts the cell into an antibody-producing cell
• DIt permanently arrests the cell in G₁ phase

Answer: Tumour-suppressor genes normally slow the cell cycle and trigger apoptosis of abnormal cells. If they are inactivated (by mutation or by hypermethylation silencing them), this control is lost and cells may divide uncontrollably, contributing to tumour formation.

A cell that can divide and differentiate into any cell type of the organism, including the cells of the placenta and extra-embryonic tissues, is described as:

• Amultipotent
• Btotipotent✓
• Cpluripotent
• Dunipotent

Answer: Totipotent cells (e.g. the zygote and very early embryo cells) can differentiate into every cell type, including the extra-embryonic/placental tissues. Pluripotent cells can form all body cell types but not the placenta; multipotent cells form a limited range.

During cell specialisation, different cell types in a multicellular organism have the same genes but different structures and functions. This is because:

• Aeach cell type contains only the genes it needs
• Bcells lose the genes they do not need as they specialise, so the genome shrinks each time a cell divides
• Conly certain genes are expressed (switched on) in each cell type, so different proteins are made✓
• Devery gene is transcribed in every cell at the same rate

Answer: Specialised cells contain the full genome but only express a subset of genes. Differential gene expression (controlled by transcription factors and epigenetic modifications) determines which proteins are produced, giving each cell type its distinct structure and function.

Adult (somatic) stem cells found in bone marrow can form red blood cells, white blood cells and platelets, but not nerve or muscle cells. These stem cells are best described as:

• Atotipotent
• Bpluripotent
• Cmultipotent✓
• Dnon-specialised but unable to divide

Answer: Bone-marrow (haematopoietic) stem cells can differentiate only into a limited range of related cell types (the blood cells), so they are multipotent. Totipotent and pluripotent cells can form a far wider range of cell types.

What is a totipotent cell able to do?

• ADifferentiate into any cell type except placental tissue
• BDifferentiate into a limited range of related cell types
• CDifferentiate only into cells of the tissue it came from
• DDifferentiate into any cell type including placental tissue✓

Answer: Totipotent cells can form every cell type plus the extra-embryonic tissues, and exist only for a short time in early development. Pluripotent cells can form any body cell but not placental tissue; multipotent and unipotent are progressively more restricted.

How does a transcription factor increase expression of a gene?

• AIt binds to the promoter region and helps RNA polymerase attach✓
• BIt binds to the promoter region and blocks RNA polymerase attaching
• CIt binds to the mRNA transcript and prevents it being translated
• DIt binds to the ribosome and speeds up formation of peptide bonds

Answer: Activating transcription factors bind a specific DNA sequence near the gene and recruit RNA polymerase, raising the rate of transcription. Repressors bind similarly but block it — which is the second option here.

How does oestrogen influence transcription?

• AIt binds a receptor which then acts as an RNA polymerase
• BIt binds a receptor which then acts as a transcription factor✓
• CIt enters the nucleus and directly forms mRNA from DNA
• DIt attaches to mRNA and prevents translation occurring

Answer: Being lipid-soluble, oestrogen crosses the membrane and binds a receptor in the cytoplasm. The hormone-receptor complex enters the nucleus, binds DNA and acts as a transcription factor. It does not synthesise RNA itself.

What is the effect of increased methylation of a gene's promoter?

• ATranscription is increased and the gene is expressed
• BThe DNA base sequence of the gene is permanently altered
• CThe gene is physically removed from the chromosome
• DTranscription is suppressed and the gene is silenced✓

Answer: Methyl groups added to the promoter stop transcription factors binding, switching the gene off. It is epigenetic — the base sequence itself is unchanged, which is why the effect can in principle be reversed.

What effect does decreased acetylation of histones have?

• AChromatin loosens and transcription is increased
• BThe DNA base sequence is permanently altered
• CIntrons are retained within the mature mRNA
• DChromatin condenses and transcription is reduced✓

Answer: Removing acetyl groups makes histones more positively charged, so they bind the negatively charged DNA more tightly. The chromatin condenses, transcription factors cannot reach the DNA and expression falls.

How does siRNA reduce gene expression?

• AIt leads to the breakdown of a specific DNA molecule
• BIt leads to the breakdown of a specific mRNA molecule✓
• CIt adds methyl groups directly onto the gene promoter
• DIt prevents RNA polymerase from binding to the promoter

Answer: Small interfering RNA pairs with a complementary mRNA and directs an enzyme complex to cut it, so the message is destroyed before it can be translated. The gene itself is untouched — the control is post-transcriptional.

Why do cells in one organism differ despite identical genomes?

• ADifferent genes are expressed in different cell types✓
• BDifferent genes are deleted from different cell types
• CEach cell type receives a different half of the genome
• DMutations accumulate differently in each cell type

Answer: Differentiation is a matter of which genes are switched on, not which are present. A liver cell and a neurone hold the same DNA but transcribe overlapping yet distinct sets of genes.

How can a mutation in a tumour suppressor gene lead to cancer?

• AThe gene starts inhibiting cell division, so division stops completely
• BThe gene stops inhibiting cell division, so division continues unchecked✓
• CThe gene begins producing far more growth factor than is required
• DThe gene is transcribed into mRNA that cannot be translated

Answer: Tumour suppressor genes normally slow the cycle and trigger apoptosis in damaged cells. Losing that brake allows unchecked division. Oncogenes work the other way — a mutated proto-oncogene becomes permanently active, driving division on.

What is the epigenome?

• AChemical modifications to DNA and histones affecting expression✓
• BChemical modifications to mRNA affecting its rate of translation
• CThe complete DNA base sequence of an individual organism
• DThe complete set of proteins produced by a cell at one time

Answer: The epigenome is the layer of methylation and histone modification sitting on top of the genome, controlling which genes are accessible. It responds to environment and can be inherited through cell division — and sometimes between generations.