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:

• Arestriction enzymes
• BDNA polymerases
• Cribosomal 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 that activates a second messenger
• BIt binds directly to RNA polymerase in the cytoplasm
• CIt is converted into 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 chromosome

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
• BIt causes the histones to leave the nucleus
• CIt directly destroys RNA polymerase
• 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 gene's promoter and block transcription factors
• BThey add methyl groups to the DNA of the gene
• 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 at the ribosome

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
• Buniversal
• Cdegenerate (more than one codon can code for the same amino acid)✓
• Dread in triplets

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 always removes a whole amino acid from the protein
• BA deletion causes a frameshift, altering every codon downstream of the mutation✓
• CA substitution cannot change any amino acids
• DA deletion only affects non-coding 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 can no longer repair its DNA
• 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 the production of proteins 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 a different set of genes
• Bcells lose the genes they do not need as they specialise
• 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.